Unit IV- Animal Physiology

1. Comparative muscle structure and function

Different Types, Different Functions

Muscle tissue is a soft tissue, and is one of the four fundamental types of tissue present in

animals. There are three types of muscle tissue recognized in vertebrates. Skeletal

muscle, or voluntary muscle, is anchored to bone by tendons, or by aponeuroses at a few

places, and is used to effect skeletal movement in activities such as locomotion and maintaining

posture. Though this postural control is generally maintained as an unconscious reflex, the

muscles responsible react to conscious control like non-postural muscles. An average adult

male is made up of 42% of skeletal muscle and an average adult female is made up of 36%,

expressed as a percentage of body mass.

Figure 1: Muscle Types. Cardiac and skeletal muscle are both striated in appearance, while

smooth muscle is not. Both cardiac and smooth muscle are involuntary while skeletal muscle

is voluntary.

Smooth muscle, or involuntary muscle, is found within the walls of organs and structures

such as the esophagus, stomach, intestines, bronchi, uterus, urethra, bladder, blood vessels, and

the arrector pili in the skin, in which it controls the erection of body hair. Unlike skeletal

muscle, smooth muscle is not under conscious control. Cardiac muscle is also an involuntary

muscle but is more akin in structure to skeletal muscle, and is found only in the heart.

Cardiac and skeletal muscles are striated, in that they contain sarcomeres and are packed into

highly regular, repeating arrangements of bundles; smooth muscle has neither attribute. While

skeletal muscles are arranged in regular, parallel bundles, cardiac muscle connects at

branching, irregular angles, called intercalated discs. Striated muscle contracts and relaxes in

short, intense bursts, whereas smooth muscle sustains longer or even near-permanent

contractions.

The density of mammalian skeletal muscle tissue is about 1.06 kg/liter. This can be contrasted

with the density of adipose tissue (fat), which is 0.9196 kg/liter. This makes muscle tissue

approximately 15% denser than fat tissue.

Skeletal muscles are voluntary, striated muscles that allow movement of an organism by the

deliberate generation of force . The action a skeletal muscle generates is determined by the

origin and insertion locations. The cross-sectional area of a muscle (rather than volume or

length) determines the amount of force it can generate by defining the number of sarcomeres

which can operate in parallel. The amount of force applied to the external environment is

determined by lever mechanics, specifically the ratio of in lever to out lever. For example,

moving the insertion point of the biceps more distally on the radius (farther from the joint of

rotation) would increase the force generated during flexion (and, as a result, the maximum

weight lifted in this movement), but decrease the maximum speed of flexion. Moving the

insertion point proximally (closer to the joint of rotation) would result in decreased force but

increased velocity. This can be most easily seen by comparing the limb of a mole to a horse:

In the former, the insertion point is positioned to maximize force (for digging), while in the

latter, the insertion point is positioned to maximize speed (for running).

In addition to voluntary contractions of skeletal muscle, involuntary muscle also contracts in a

similar fashion but does so involuntarily. Smooth muscle is responsible for movement of food

through the digestive system via peristalsis and regulates the diameter of blood vessels,

determining how much blood flows through the vessels. Cardiac muscle is responsible for

contraction of the heart . The contraction of cardiac muscle of the heart is coordinated such that

the entire heart beats in a controlled, uniform manner, ensuring blood is efficiently pumped

from the chambers. Cardiac and smooth muscle contraction occurs without conscious thought

and is necessary for survival.

Cardiac muscle is striated, similar to skeletal muscle, but beats involuntarily. The cells

beat in unison as a result of unique gap junctions between the muscle cells.

Diagram of contraction of smooth muscle fiber

showing peristalsis

Skeletal muscle fibers can be characterized by their metabolic processes and corresponding

physiological traits.

Signaling Pathways that Regulate Skeletal Muscle Fiber-type Phenotype

Exercise-induced signaling pathways in skeletal muscle that determine specialized

characteristics of slow-twitch and fast-twitch muscle fibers.

Oxidative fibers rely on aerobic respiration to fuel muscle contractions, and consist of slow-

twitch (Type I) fibers, which are characterized as muscles with long contraction duration,

associated with endurance. Slow-twitch fibers are used to maintain posture. They are usually

found in red muscles, indicative of the large concentration of myoglobin providing a steady

supply of oxygen to them. The red muscles use oxidative phosphorylation to obtain ATP.

Oxidative phosphorylation occurs in the red muscles as the process requires a lot of oxygen,

and the red muscles contain high amounts of myoglobin. The process is slower than glycolysis,

but much more efficient, which is why slow-twitch muscles do not tire easily. Also, slow-

twitch fibers contain less sarcoplasmic reticulum, facilitating a slower release of calcium,

regulating muscle contraction at slower rates.

Glycolytic fibers rely on glycolysis to fuel muscle contractions and consist of fast-twitch (Type

II) fibers, which are characterized by fast muscle contractions of short duration. Fast-twitch

fibers are constituents of white muscles and have less myoglobin due to their primary reliance

on glycolysis (anaerobic respiration) to fuel muscle contractions. Although glycolysis is very

quick, it is also inefficient at producing ATP. Glycolysis produces lactic acid as a byproduct,

which leads to fatigue. The use of the glycogen cycle is the reason why fast-twitch muscles tire

out quickly.

There is some evidence that the proportion of fast-twitch versus slow-twitch muscles of an

individual is partly genetic in nature. That is, we are born with a unique proportion of such

muscles that suit us to particular types of physical activity. This is not without debate, however.

Regardless, concentrated exercise that prioritizes one type of muscle fiber use over the other,

can lead to muscle hypertrophy (increase in size), improving an individual’s ability to perform

related physical activities.

Muscle fiber generates tension through the action of actin and myosin cross-bridge cycling.

While under tension, the muscle may lengthen, shorten, or remain the same. Although the term

contraction implies shortening, when referring to the muscular system, it means muscle fibers

generating tension with the help of motor neurons. Several types of muscle contractions occur

and they are defined by the changes in the length of the muscle during contraction.

Isotonic Contractions

Isotonic contractions maintain constant tension in the muscle as the muscle changes length.

This can occur only when a muscle’s maximal force of contraction exceeds the total load on

the muscle. Isotonic muscle contractions can be either concentric (muscle shortens) or eccentric

(muscle lengthens).

Concentric Contractions

A concentric contraction is a type of muscle contraction in which the muscles shorten while

generating force. This is typical of muscles that contract due to the sliding filament mechanism,

and it occurs throughout the muscle. Such contractions also alter the angle of the joints to which

the muscles are attached, as they are stimulated to contract according to the sliding filament

mechanism.

This occurs throughout the length of the muscle, generating force at the musculo-tendinous

junction; causing the muscle to shorten and the angle of the joint to change. For instance, a

concentric contraction of the biceps would cause the arm to bend at the elbow as the hand

moves from near to the leg to close to the shoulder (a biceps curl). A concentric contraction of

the triceps would change the angle of the joint in the opposite direction, straightening the arm

and moving the hand toward the leg.

Eccentric Contractions

An eccentric contraction results in the elongation of a muscle. Such contractions decelerate the

muscle joints (acting as “brakes” to concentric contractions) and can alter the position of the

load force. These contractions can be both voluntary and involuntary. During an eccentric

contraction, the muscle elongates while under tension due to an opposing force which is greater

than the force generated by the muscle. Rather than working to pull a joint in the direction of

the muscle contraction, the muscle acts to decelerate the joint at the end of a movement or

otherwise control the repositioning of a load.

This can occur involuntarily (when attempting to move a weight too heavy for the muscle to

lift) or voluntarily (when the muscle is “smoothing out” a movement). Over the short-term,

strength training involving both eccentric and concentric contractions appear to increase

muscular strength more than training with concentric contractions alone.

Isometric Contractions

In contrast to isotonic contractions, isometric contractions generate force without changing the

length of the muscle . This is typical of muscles found in the hands and forearm: the muscles

do not change length, and joints are not moved, so force for grip is sufficient. An example is

when the muscles of the hand and forearm grip an object; the joints of the hand do not move,

but muscles generate sufficient force to prevent the object from being dropped.

Force-length relationship in muscle: Muscle length versus isometric force.

2. Contraction of Muscles

Skeletal muscles contract and relax to mechanically move the body. Messages from the nervous

system cause these muscle contractions. The whole process is called the mechanism of muscle

contraction and it can be summarized in three steps:

(1) A message travels from the nervous system to the muscular system, triggering chemical

reactions.

(2) The chemical reactions lead to the muscle fibers reorganizing themselves in a way that

shortens the muscle--that’s the contraction.

(3) When the nervous system signal is no longer present, the chemical process reverses, and

the muscle fibers rearrange again and the muscle relaxes.

Let’s look a little more closely at the steps in the mechanism of muscle contraction.

1. A Muscle Contraction Is Triggered When an Action Potential Travels Along the Nerves

to the Muscles

Muscle contraction begins when the nervous system generates a signal. The signal, an impulse

called an action potential, travels through a type of nerve cell called a motor neuron. The

neuromuscular junction is the name of the place where the motor neuron reaches a muscle cell.

Skeletal muscle tissue is composed of cells called muscle fibers. When the nervous system

signal reaches the neuromuscular junction a chemical message is released by the motor neuron.

The chemical message, a neurotransmitter called acetylcholine, binds to receptors on the

outside of the muscle fiber. That starts a chemical reaction within the muscle.

2. Acetylcholine Is Released and Binds to Receptors on the Muscle Membrane

A multistep molecular process within the muscle fiber begins when acetylcholine binds to

receptors on the muscle fiber membrane. The proteins inside muscle fibers are organized into

long chains that can interact with each other, reorganizing to shorten and relax. When

acetylcholine reaches receptors on the membranes of muscle fibers, membrane channels open

and the process that contracts a relaxed muscle fibers begins:

• Open channels allow an influx of sodium ions into the cytoplasm of the muscle fiber.

• The sodium influx also sends a message within the muscle fiber to trigger the release

of stored calcium ions.

• The calcium ions diffuse into the muscle fiber.

• The relationship between the chains of proteins within the muscle cells changes, leading

to the contraction.

3. Muscle Fibers Relax When the Nervous System Signal Is No Longer Present

When the stimulation of the motor neuron providing the impulse to the muscle fibers stops, the

chemical reaction that causes the rearrangement of the muscle fibers' proteins is stopped. This

reverses the chemical processes in the muscle fibers and the muscle relaxes.

3. Sliding Filament Theory of Muscle Contraction

The mechanism of muscle contraction is explained by sliding filament model. This theory was

proposed by H.E Huxley and J. Hanson, and A. F. Huxley and R. Niedergerke in 1954.

The arrangement of actin and myosin myofilament within a sarcomere is crucial in the

mechanism of muscle contraction. It is proposed that muscle contracts by the actin and myosin

filaments sliding past each other. For analogy, muscle contraction by sliding filament model is

equivalent to interlocking fingers, pushing them together shortens the distance.

As sarcomere is the unit of muscle contraction, its length contracts resulting in whole muscle

contraction. During contraction, length of A-band (Dark band) remains same whereas length

of I-band (Light band) and H-zone gets shorter.

Actin myofilament:

▪ An actin myofilament is made up of actin molecule, tropomyosin and troponin

complex. Troponin is composed of three sub-units (troponin I, T and

C). Tropomyosin form two helical strand which are wrapped around actin

molecules (G-actins) longitudinally in thin twisted stranded form.

▪ Each G-actin is attached with an ATP molecule. The whole assembly of actin

molecules is known as F-actin (Fibrous actin).

▪ Tropomyosin switches ON or OFF the muscle contraction mechanism.

▪ Troponin complex is a globular protein which binds to tropomyosin and calcium

ions.

Myosin myofilament:

▪ A myosin myofilament consists of two distinct region, a long rod-shaped tail

called myosin rod and two globular intertwined myosin head.

▪ The globular head appear at interval along the myosin myofilament, projecting

from the sides of the filament.

▪ The myosin head can attach to the neighboring acting filament where actin and

myosin filaments overlaps.

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Figure: Actin and Myosin myofilament

Mechanism of Muscle contraction:

▪ When the nerve impulse from brain and spinal cord are carried along motor

neuron to neuromuscular junction, Ca++ ions are released in the terminal axon.

Increases calcium ion concentration stimulates the release of neurotransmitter

(Acetylcholine) in the synaptic cleft. The neurotransmitter binds to the receptor

on the sarcolemma and depolarization and generate action potential across

muscle fiber for muscle contraction. The action potential propagates over entire

muscle fiber and move to the adjacent fibers along transverse tubules. The action

potential in transverse tubules causes the release of calcium ion from

sarcoplasmic reticulum, which stimulate for muscle contraction.

The sequences of muscle contraction explained by sliding filament theory are as follows

▪

Figure: diagrammatic representation of muscle contraction mechanism

1. Blocking of myosin head:

▪ Actin and myosin overlaps each other forming cross bridge. The cross bridge is

active only when myosin head attached like hook to the actin filament.

▪ When muscle is at rest, the overlapping of actin filament to the myosin head is

blocked by tropomyosin. The actin myofilament is said to be in OFF position

2. Release of calcium ions:

▪ Nerve impulse causing depolarization and action potential in the sarcolemma

trigger the release of calcium ions from sarcoplasmic reticulum.

▪ The calcium ion then binds with the troponin complex on the actin myofilament

causing displacement of troponin complex and tropomyosin from its blocking

site exposing myosin binding site.

▪ As soon as the myosin binding site is exposed, myosin head cross bridge with

actin filament. Now, the actin myofilament is said to be in ON position.

3. Active Cross-bridge formation:

▪ When myosin head attached like hooks to the neighboring actin filament, active

cross bridge is formed. The cross bridge between actin and myosin filament acts

as an enzyme (Myosin ATPase).

▪ The enzyme Myosin ATpase hydrolyses ATP stored into ADP and inorganic

phosphate and release energy. This released energy is used for movement of

myosin head toward actin filament. The myosin head tilts and pull actin filament

along so that myosin and actin filament slide each other. The opposite end of

actin myofilament within a sarcomere move toward each other, resulting in

muscle contraction.

▪ After sliding the cross bridge detached and the actin and myosin filament come

back to original position. The active cross bridge form and reform for 50-100

time within a second using ATP in rapid fashion. Therefore, muscle fiber consists

of numerous mitochondria.

▪ In muscle contraction, sarcomere can contracts by 30-60% of its length

4. Significance of Membrane potentials

Membrane potential (also transmembrane potential or membrane voltage) is the

difference in electric potential between the interior and the exterior of a biological cell. For the

exterior of the cell, typical values of membrane potential, normally given in units

of millivolts and denoted as mV, range from –40 mV to –80 mV.

All animal cells are surrounded by a membrane composed of a lipid

bilayer with proteins embedded in it. The membrane serves as both an insulator and a diffusion

barrier to the movement of ions. Transmembrane proteins, also known as ion transporter or ion

pump proteins, actively push ions across the membrane and establish concentration gradients

across the membrane, and ion channels allow ions to move across the membrane down those

concentration gradients. Ion pumps and ion channels are electrically equivalent to a set

of batteries and resistors inserted in the membrane, and therefore create a voltage between the

two sides of the membrane.

Almost all plasma membranes have an electrical potential across them, with the inside usually

negative with respect to the outside.[1] The membrane potential has two basic functions. First,

it allows a cell to function as a battery, providing power to operate a variety of "molecular

devices" embedded in the membrane.[2] Second, in electrically excitable cells such

as neurons and muscle cells, it is used for transmitting signals between different parts of a cell.

Signals are generated by opening or closing of ion channels at one point in the membrane,

producing a local change in the membrane potential. This change in the electric field can be

quickly affected by either adjacent or more distant ion channels in the membrane. Those ion

channels can then open or close as a result of the potential change, reproducing the signal.

In non-excitable cells, and in excitable cells in their baseline states, the membrane potential is

held at a relatively stable value, called the resting potential. For neurons, typical values of the

resting potential range from –70 to –80 millivolts; that is, the interior of a cell has a negative

baseline voltage of a bit less than one-tenth of a volt. The opening and closing of ion channels

can induce a departure from the resting potential. This is called a depolarization if the interior

voltage becomes less negative (say from –70 mV to –60 mV), or a hyperpolarization if the

interior voltage becomes more negative (say from –70 mV to –80 mV). In excitable cells, a

sufficiently large depolarization can evoke an action potential, in which the membrane

potential changes rapidly and significantly for a short time (on the order of 1 to 100

milliseconds), often reversing its polarity. Action potentials are generated by the activation of

certain voltage-gated ion channels.

In neurons, the factors that influence the membrane potential are diverse. They include

numerous types of ion channels, some of which are chemically gated and some of which are

voltage-gated. Because voltage-gated ion channels are controlled by the membrane potential,

while the membrane potential itself is influenced by these same ion channels, feedback loops

that allow for complex temporal dynamics arise, including oscillations and regenerative events

such as action potentials.

5. Nerve impulse Propagation

Definition of Nerve Impulse:

The electrochemical wave that travels along nerve fibre and stimulates muscles, glands or other

nerve cells is called nerve impulse.

Typical structure of neuron:

Neuron is the structural and functional unit of nervous system. It consists of a nerve cell body

or soma and two types of processes-axon and dendrite (Fig. 8.29).

Soma:

It is an irregular-shaped structure in the centre of which there lies a spherical nucleus with

prominent nucleolus and Nissl granules. It also contains mitochondria, Golgi body, ribosome

and ER etc.

Dendrite:

It is the process of the cell body that carries impulse towards the cell body. It is usually short

with many branches and contains Nissl granules.

Axon:

It is the process of a nerve cell body that carries impulse away from it. It is usually single, long

slender process and sometimes branched and contains axoplasm, neuro-fibril, etc. It terminates

into branches with terminal buttons.

Classification of stimulus:

(a) Subliminal stimulus:

Which can produce the local excitatory state (LES) only?

(b) Threshold value of stimulus:

Which can produce or transform the LES to action potential?

Propagation of Nerve Impulse:

The propagation of nerve impulse involves two major parts – A. Origin/stimulation of nerve

impulse, B. Propagation/ travelling of nerve impulse.

A. Origin of Nerve impulse:

In resting nerve cells, the surface is positively charged and the interior is negatively charged.

When the surface is stimulated the stimulated point becomes negative. The fluids both inside

and outside the cell are electrolytic solution containing 150-160m Eq/litre.

Positive ions and negative ions are accumulated along the outer and inner surface of the cell

membrane, respectively. This is achieved by Na+ outside and K+ inside the cell membrane, and

because Na+ is placed above the K+ in the electrochemical series.

Development of local excitatory state and Development of action potential:

When stimulation is applied on the nerve cell, external Na+ rushes inside the cell making the

inner surface positively charged. The amount of Na+ is not sufficient to generate action

potential and returns to the outside immediately, causing a closed circuit.

Resting potential:

In resting state the nerve fibres remain in polarised state and the membrane potential lies within

-70 mv. Na+ concentration outside the membrane is higher than that of inside and

K+ concentration inside the membrane is higher than that of outside. K+ can permeate through

the membrane at resting condition but the Na+ cannot permeate.

State of De-polarisation:

Permeability of Na+ to membrane is increased only after stimulation; causing de-polarisation.

The tremendous increase in Na+ conductance during this period is known as activation of

membrane. After an initial slow rise, de-polarisation wave overshoots rapidly and can reach

the iso-potential line (above zero line) to approximately +35 mv (Fig. 8.30).

State of re-polarisation:

After reaching the iso-potential line K+ begins to come out from inside the membrane, causing

outside to be positive again. This is called re-polarisation.

Spike potential:

The periodic rise of de-polarisation wave and rapid fall of re-polarisation wave are known as

spike potential.

Negative after potential:

At approximately 2/3rd of the polarisation, the rate of fall is being abruptly slowed down. This

slower fall is known as negative after potential.

Positive after potential:

With the disappearance of the negative after potential, although the rising membrane potential

is achieved, yet the resting ionic status is not established. It is achieved by the active Na+ pump

mechanism, which causes the positive after potential. At the same time K+ travels back to the

inside of the membrane.

B. Propagation/travelling of nerve impulse:

1. Propagation on non-medulated nerve fibre:

According to the membrane theory, nerve impulse is a propagated wave of de-polarisation.

i) When the fibre is excited at a point, the polarity is reversed. This reversed polarity is due to

increased permeability of Na+ to the membrane, which develops de-polarisation wave.

ii) A local circuit current flows between the de-polarised membrane and the resting membrane

areas.

iii) Positive current flows inward through the de-polarised membrane and outward through the

resting membrane and in this way circuit is completed.

iv) The local de-polarisation current then exits the adjacent portion of the membrane

progressively more and more de-polarisation.

v) The de-polarisation wave travels in all direction along the entire length of the nerve fibre.

2. Propagation in myelinated nerve fibre: Salutatory conduction:

In the myelinated nerve fibre conduction depends upon the similar pattern of circular current

flow. Myelin sheath is an effective insulator. Ions cannot pass along the myelin sheaths but

nodes of Ranvier permeate ions through it more easily. For this reason the impulse is

transmitted from node to node rather than continuously along the entire of the nerve fibre (Fig.

8.32).

The de-polarisation in myelinated action jumps from one node of Ranvier to the next. This

jumping or leaping of de-polarisation from node to node is known as saltatory conduction.

Rate of Conduction of Nerve Impulse:

The basic principle of origin and propagation of nerve impulse is same, both in non-medulated

and myelinated nerve fibres but the saltatory mechanism of conduction in myelinated nerve

fibre increases the velocity of conduction more than 500 times.

The rate of conduction of a nerve impulse increases with an increase in the cross sectional

diameter of the neuron and with increasing thickness of the myelin sheath. The rate of trans-

mission for a given neuron is a constant. Table 8.8 gives an idea about rate of nerve impulse

conduction through different nerves of various animals.

6. Synoptic transmission Introduction

Humans and other vertebrates have developed a highly efficient system of communication, the

nervous system. It is a network of interconnected neurons that are capable of generating and

transmitting nerve impulses. The communication process is based on the successful

transmission of nerve impulses from one neuron to the other.

Neurons are connected via specialized structures called synapses. The transmission of a nerve

impulse or action potential from one neuron to another neuron or non-neuron cell, across the

synapse, is called synaptic transmission.

The process of synaptic transmission can be easily understood after studying the structure and

the type of synapses involved. In this article, we will discuss the structure and types of

synapses, the process of synaptic transmission, the role of neurotransmitters, the effects of

drugs, and clinical conditions associated with the synaptic transmission.

Types of Synapses

Not all the synapses found in the body are the same. Based on the mode of synaptic

transmission, the synapses found in the human body are divided into two types; chemical

synapses and electrical synapses.

Chemical Synapses

These are the most abundant synapses found in the body. The two neurons are joined via a

synaptic cleft. One of the two cells secretes neurotransmitters into the cleft. These chemical

messengers diffuse through the cleft and act on the receptors present on the other cell.

As chemical messengers i.e. neurotransmitters are used for transmission of nerve impulses

across a synapse, such synapses are called chemical synapses.

The detailed structure of such synapses will be discussed in detail.

Electrical Synapses

In some cases, the two cells are connected via gap junctions. The cytoplasm of these cells is

connected in such a way that ions can freely diffuse among the cells. the action potential

generated in one cell is transmitted to the next cell by the flow of ions.

As ions or electric currents are used for the transmission of action potential among the cells,

such synapses are called electrical synapses. They are found among the cardiac muscles and

some smooth muscle cells.

Structure of a Chemical Synapse

Understanding the structure of a chemical synapse will help us grab the concept of synaptic

transmission.

A chemical synapse has three major components; pre-synaptic terminal, synaptic cleft, and

post-synaptic terminal.

Pre-synaptic Terminal

It is the axon terminal of the pre-synaptic neuron. The axon terminal makes a dilation

called axon bouton. It is connected to the post-synaptic neuron or cell via the synaptic cleft.

The pre-synaptic terminal has multiple adaptations to release neurotransmitter when the action

potential reaches the axon bouton. Neurotransmitters are kept stored in the axonal terminal in

the form of vesicles. Certain calcium channels are present in the plasma membrane. Certain

channels for the release and uptake of neurotransmitters are also present.

Synaptic Cleft

It is the space between the pre-synaptic and post-synaptic cells. the neurotransmitters released

by the pre-synaptic terminal diffuse through this space to act on the post-synaptic cells.

The size of the synaptic cleft is of the order of 20 nm. This small size allows the

neurotransmitters to rapidly pile up and diffuse through the cleft.

This space between the two cells also has certain enzymes that can cause degradation of

neurotransmitters. It helps remove the neurotransmitters when they have done their action.

Post-synaptic Terminal

The post-synaptic terminal may be a neuron or non-neuronal cell. It contains receptors for

neurotransmitters that are linked to some ion channels. The binding of neurotransmitters to

these receptors results in the opening of ion channels, the ion diffuse across the cell, and an

action potential is generated in the post-synaptic cell.

The post-synaptic receptors are usually located in an invagination of the cell membrane called

synaptic gutter or junctional folds.

Process of Synaptic Transmission

The process of synaptic transmission involves two steps; release of neurotransmitter from pre-

synaptic cell and generation of an action potential in the post-synaptic cell.

Release of Neurotransmitter

Neurotransmitters are released by the pre-synaptic cell when an action potential reaches the

terminal. The process is as follows;

• Specialized voltage-gated calcium channels are located in the pre-synaptic

terminal.

• When the action potential reaches the axon terminal, the depolarization of

axolemma (plasma membrane of axons) causes the opening of calcium

channels.

• Calcium ions are present in higher concentrations in the extracellular fluid

surrounding the terminal. The opening of calcium channels causes these ions to

diffuse into the axonal fiber.

• Once inside the axon terminal, calcium ions bind to some specialized proteins

located on the inner surface of the membrane called release sites.

• Binding of calcium ions to these release sites causes the synaptic vesicles to

diffuse with the terminal membrane.

• Synaptic vesicles diffuse and the neurotransmitter molecules present in them

are released into the synaptic cleft.

The number of neurotransmitters released into the cleft is proportional to the number of calcium

ions diffusing into the pre-synaptic terminal.

Generation of Action Potential

The process of synaptic transmission is completed when an action potential is generated in the

post-synaptic cell. It involves the following steps.

• Neurotransmitters diffuse across the synaptic cleft and reach the junctional folds

on the post-synaptic cell.

• Here, the neurotransmitters bind to the membrane receptors and activate them.

• The activation of receptors causes the opening of ion channels.

• Sodium ions present abundantly in the surrounding fluid rapidly enter the cell

down the concentration gradient.

• The diffusion of sodium ions into the cell causes depolarization and a receptor

potential is generated.

• If the receptor potential is greater than the threshold, an action potential is

generated in the post-synaptic cell.

The strength of receptor potential depends on the number of neurotransmitters binding to the

receptors.

Removal of Neurotransmitters

In most of the cases, the number of neurotransmitters released during synaptic transmission is

greater than the requirements. Once an action potential is generated, the excess

neurotransmitters must be removed from the cell. If the extra neurotransmitters are not

removed, they will cause continuous excitation of the post-synaptic cell.

There are two ways to remove extra neurotransmitters;

• Breakdown enzymes are present in the synaptic cleft. They cleave the

neurotransmitters to rapidly decrease their concentration in the synapse. The

breakdown products may be taken up by the pre-synaptic neuron to make new

neurotransmitters.

• Certain protein channels are present in the pre-synaptic terminal. They use ATP

to actively pump the neurotransmitters back into the axon. This also helps to

rapidly decrease the concentration of neurotransmitters.

The reabsorbed neurotransmitters are again packed into the synaptic vesicle and are ready to

be released again during the next cycle.

Neurotransmitters

These are the chemical messengers that are involved in the process of synaptic transmission in

chemical synapses. Their study is necessary to completely understand the synaptic

transmission.

Here we will discuss briefly the synthesis and types of neurotransmitters.

Synthesis

Neurotransmitters are either amino acids or peptides in nature. They are made by the rough

endoplasmic reticulum present in the cell body of the pre-synaptic neuron.

The neurotransmitters are then packed into excretory vesicles called synaptic vesicles. The

synaptic vesicles are formed by the Golgi bodies and are stored in the pre-synaptic terminal.

Types

Not every neurotransmitter released into the synapse causes an action potential in the post-

synaptic cell. Sometimes, they can also block nervous transmission.

Based on their function, there are two types of neurotransmitters.

Excitatory Neurotransmitters

These can cause the excitation of the post-synaptic cells. Binding of such neurotransmitters to

the receptors causes;

• Increased conduction through the sodium channels by opening them

• Decreased conduction through the potassium channels by blocking them

Both these changes cause depolarization of the cell and an action potential is generated.

Examples of excitatory neurotransmitters include norepinephrine, acetylcholine, and

dopamine, etc.

Inhibitory Neurotransmitters

These serve to block synaptic transmission. The following changes take place in a post-synaptic

cell when an inhibitory neurotransmitter binds to its receptors.

• Increased conduction through the potassium channels so that potassium ions

diffuse out of the cell

• Decreased conduction through the sodium ions so that no sodium ion enters the

cell

All these changes make the cell hyperpolarized and no action potential is generated. As a result,

synaptic transmission is blocked.

Examples of inhibitory transmitters include GABA, serotonin, and dopamine in some cases.

Drugs Action

Sometimes, there is a medical need to enhance or suppress synaptic transmission. For example,

in chronic pain conditions, synaptic transmission is blocked to treat pain. Certain drugs act on

synapse and are responsible for modifications in synaptic transmission. Some of these drugs

are as mentioned below.

Curare Drugs

These drugs are used for complete blockage of action potential transmission at some synapses.

They are the acetylcholine antagonists. Curare drugs bind to acetylcholine receptors and block

their activation. The receptors are not stimulated even when abundant acetylcholine is present

in the synaptic cleft.

Some examples of curare drugs are atracurium, pancuronium, and vecuronium, etc. These are

the non-depolarizing muscle reactants, as they prevent the depolarization of post-synaptic cells.

Atracurium is used as a skeletal muscle relaxant during surgery or mechanical ventilation.

Morphine

It is a powerful pain-killer used in extreme situations. Morphine inhibits synaptic transmission

of pain signals by activating meu-receptors.

Meu-receptors cause increased potassium efflux out of the cell and decreased influx of calcium

and sodium ions. The cell becomes hyperpolarized and the synaptic transmission is blocked.

Acetylcholine esterase Inhibitors

Acetylcholine esterase is an enzyme present in the synaptic cleft that cleaves acetylcholine into

choline and acetic acid. The action of this enzyme is necessary to remove excess acetylcholine

and end the transmission process after one cycle.

The inhibitors of this enzyme are used to increase the concentration of acetylcholine in the

synaptic cleft. These drugs are used in Myasthenia gravis, glaucoma, and to increase the

motility of digestive and urinary systems.

Examples of these drugs include physostigmine, neostigmine, rivastigmine, etc.

Strychnine

It is a poisonous drug that blocks synaptic transmission at the motor endplate (synapse between

skeletal muscle fiber and a motor neuron). It blocks the glycine receptors on alpha motor

neurons in the spinal cord. Thus, there is no more inhibitory effect of glycine and uncontrolled

muscle contractions occur. This leads to muscle spasm.

Alcohol

Alcohol plays a role in the transmission of inhibitory synaptic signals. It mimics the action of

inhibitory neurotransmitter GABA, bi binding to GABAA receptors. As a result, the inhibitory

effect of GABA is enhanced. The post-synaptic neuron becomes hyperp[olarized due to this

action.