Nerve physiology 3rd lecture

By

Dr. Mudassar Ali Roomi (MBBS, M. Phil)

Inhibition of Excitability- “Stabilizers” and Local Anesthetics

• the factors that decrease nerve excitability are called as membrane-stabilizing factors.

• Calcium

• local anesthetics: • Examples: procaine and

tetracaine.

• Mechanism of action of local anesthetics: acts directly on the activation gates of the sodium channels, making it much more difficult for these gates to open.

Role of calcium in membrane excitability

• Hypercalcemia decrease membrane excitability.***

• In hypercalcemia decreased excitability of membrane (also severe constipation).**

• Hypocalcemia increased excitability of nervous tissue.**

• Inner side of sodium channels is highly negatively charged.

• Calcium ions bind with negative inner surface of sodium channels complete closure of activation gates of these channels at rest.

• So, Calcium (normal levels) stabilizes the membrane and decreases its exciability.

Why tetany occurs in hypocalcemia??

• Decreased calcium in ECF no complete closure of activation gates of sodium channels at rest sodium ions leak into membrane from ECF hypo-polarization (membrane potential becomes less negative & near to threshold) & on slight stimulation action potential (tetany).

Why tetany is aggravated in alkalosis?

• Protein molecules behave as acid (proton donors become anions) in alkaline pH.

• At 7.4 (alkaline body pH), protein anions bind positive ions (sodium, potassium, calcium).

• Protein bound form of calcium increases & ionic form thus decreases tetany.

NERVE FIBER /

SKELETAL MUSCLE

CARDIAC

MUSCLE

SMOOTH

MUSCLE

Multiple peripheral

nuclei.

Single central

nucleus.

Single central

nucleus.

Triad is at the

junction of A & I

bands.

Intercalated discs /

gap junctions are at

the level of Z

membranes. (Diad)

In some places

(intestine), randomly

distributed thick &

thin filaments

interdigitate.

Few mitochondria.

Major source of energy

is CHO.

Glycolysis Citric acid

cycle.

More mitochondria

(25% mass). Major

source of energy is

fat (60%) at rest.

Fewer mitochondria.

Mostly glycolytic

metabolism.

Propagation of action potential

• Propagation of action potential is an example of positive feedback mechanism.

• velocity (m/sec) of myelinated fiber = diameter (in mm) x 4.5

• velocity of (m/sec) unmyelinated fiber = Square root of diameter

Propagation of action potential in un-myelinated nerve fibers

• Point to point conduction. • Local circuit of current is formed

between depolarized point & adjacent polarized point.

• Current flowing out through depolarized point, activates Na+ channels at polarized point depolarization action potential.

• Then a new circuit of current is formed between this depolarized point & adjacent polarized point.

• In case of unmyelinated nerve fiber, velocity of conduction is slow, because it is point to point.

• Synapses only allow propagation between pre synaptic to post synaptic neuron inside the body (law of forward conduction). but in vitro it is in both directions.

Myelination

• Schwann cells surround the nerve

axon forming a myelin sheath

• Sphingomyelin decreases

membrane capacitance and ion flow

5,000-fold

• Sheath is interrupted every 1-3 mm

: node of Ranvier

Figure 5-16; Guyton & Hall

Propagation of action potential along a myelinated nerve fiber

SALTATORY CONDUCTION

• Saltare: to jump • Node to node

conduction. • Internodes are

myelinated and act as insulators.

• Myelin sheath is absent at the nodes of Ranvier & neurilemma at the nodes has got ion channels.

Local circuit of saltatory conduction

• depolarized node adjacent polarized node conduction of current through axoplasm and ECF next node is also depolarized

Benefits of saltatory conduction

1. Faster velocity of conduction in large myelinated nerve fibers e.g A-alpha fibers (120 m/sec ). It is very slow (0.5-2 m/sec) in small unmyelinated nerve fibers e.g. type C fibers.

2. Less energy expenditure due to less ionic change

3. Insulation of nerve fibers prevents the short circuiting.