Chapter 4 - Neuropharmacology

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  • 1.Neurophysiology,Neurophysiology, Neurotransmitters and theNeurotransmitters and the Nervous SystemNervous System

2. The NeuronThe Neuron The nervous system is made of nerve cells or neurons and glial cells. Glial cells are not excitable and provide metabolic and physical support for the neurons. 90% of the cells are glial cells. Neurons are excitable and control behavior 3. NeuronNeuron 4. Resting potentialResting potential 5. Resting potentialResting potential There is a potential difference between the inside and outside of as membrane. The inside is about -70 mv relative to the outside. 6. Resting PotentialResting Potential The resting potential is caused by an uneven distribution of ions (electrically charged molecules) of potassium (K+) and sodium (Na+) and chloride (Cl-). This is caused by Na+/K+ ion pumps that move 3 Na+ ions out of the cell for every 2 K+ ions it moves in. Therefore there are more +ions outside the cell than inside and the inside is negatively charged with respect to the outside 7. Ion pumpIon pump 8. Resting potentialResting potential An ion channel is a combination of large protein molecules that cross the membrane and allow specific ions to pass through at a specific rate, These allow enough leakage of ions to mostly neutralize the effect of the ion pump, but 9. Ion channelsIon channels 10. Resting potentialResting potential Forces maintaining the resting potentialForces maintaining the resting potential Diffusion pressure molecules want to moveDiffusion pressure molecules want to move from areas of high concentration to areas offrom areas of high concentration to areas of low concentration.low concentration. Electrostatic charge ions with like chargeElectrostatic charge ions with like charge are repelled and ions with a different chargeare repelled and ions with a different charge are attracted.are attracted. Operation of ion pumps and ion channels.Operation of ion pumps and ion channels. 11. Action potentialAction potential Anything that alters the functioning of the ionAnything that alters the functioning of the ion channels can change the resting potential.channels can change the resting potential. If changes cause the resting potential to beIf changes cause the resting potential to be reduced, this is calledreduced, this is called depolarization.depolarization. If the change causes an increase in the restingIf the change causes an increase in the resting potential, this is causedpotential, this is caused hyperpolarizationhyperpolarization.. 12. Action PotentialAction Potential We can insert an electrode across aWe can insert an electrode across a membrane and cause depolarization, i.e.,membrane and cause depolarization, i.e., we can depolarize the cell.we can depolarize the cell. If we reduce the resting potential past aIf we reduce the resting potential past a thresholdthreshold, the resting potential breaks, the resting potential breaks down.down. 13. Action potentialAction potential Voltage gated ion channels open and let Na+ into theVoltage gated ion channels open and let Na+ into the cell. They are driven into the cell because of diffusioncell. They are driven into the cell because of diffusion gradient and electrostatic charge.gradient and electrostatic charge. This causes the resting potential to reverse, i.e., theThis causes the resting potential to reverse, i.e., the inside the cell becomes positive.inside the cell becomes positive. Now the Na+ ion channels close and the K+ channelsNow the Na+ ion channels close and the K+ channels open and the K+ ions are driven out of the cell becauseopen and the K+ ions are driven out of the cell because of their concentration gradient and electrostatic charge.of their concentration gradient and electrostatic charge. Finally the K+ channels close and the ion pumps kick inFinally the K+ channels close and the ion pumps kick in and the resting potential returns to normal.and the resting potential returns to normal. 14. Action potentialAction potential 15. All or None LawAll or None Law Action potentials when they occur areAction potentials when they occur are always the same.always the same. Once the process is initiated, it must runOnce the process is initiated, it must run its course and nothing can stop it orits course and nothing can stop it or change itchange it 16. Transmission of action potentialsTransmission of action potentials along a membranealong a membrane When an action potential occurs at oneWhen an action potential occurs at one place on the membrane of an axon, theplace on the membrane of an axon, the surrounding membrane is depolarizedsurrounding membrane is depolarized past threshold causing an action potential.past threshold causing an action potential. This depolarizes the neighboringThis depolarizes the neighboring membrane, etc.membrane, etc. Action potentials sweep across aAction potentials sweep across a membrane as fast as 100m/secmembrane as fast as 100m/sec 17. Transmission of action potentialsTransmission of action potentials along a membranealong a membrane 18. Postsynaptic potentialsPostsynaptic potentials The membranes of dendrites and cellThe membranes of dendrites and cell bodies do not have action potentials.bodies do not have action potentials. Instead, any depolarizing stimulus causesInstead, any depolarizing stimulus causes a post synaptic potential (PSP) whicha post synaptic potential (PSP) which spreads out across the membrane. Thespreads out across the membrane. The depolarization is weaker the further it getsdepolarization is weaker the further it gets from the stimulus. When the stimulus isfrom the stimulus. When the stimulus is turned off, the PSP disappears.turned off, the PSP disappears. 19. Postsynaptic potentialsPostsynaptic potentials Postsynaptic potentials can either bePostsynaptic potentials can either be excitatory (depolarization) or inhibitory.excitatory (depolarization) or inhibitory. Excitatory and inhibitory potentials canExcitatory and inhibitory potentials can summate both in time (summate both in time (temporaltemporal summationsummation) and across the membrane) and across the membrane ((spatial summationspatial summation) .) . The net effect of summation is reflected atThe net effect of summation is reflected at the axon hillock where action potentialsthe axon hillock where action potentials are generated.are generated. 20. The synapseThe synapse Normally, cell bodies are stimulated byNormally, cell bodies are stimulated by either byeither by stimuli in the environment, e.g. sensory cellsstimuli in the environment, e.g. sensory cells like the rods and cones in the eye, orlike the rods and cones in the eye, or Connections from other nerve cells, i.e.,Connections from other nerve cells, i.e., synapsessynapses 21. The SynapseThe Synapse 22. The SynapseThe Synapse 23. SynapseSynapse Any neuron can have thousands of synapses on it 24. SynapseSynapse When an action potential arrives at theWhen an action potential arrives at the terminalterminal boutonbouton, it causes Ca++ channels to open., it causes Ca++ channels to open. This causes the vesicles to move to theThis causes the vesicles to move to the membrane and release a chemical called amembrane and release a chemical called a neurotransmitterneurotransmitter to be released into theto be released into the synaptic cleft.synaptic cleft. The neurotransmitter diffuses across the cleftThe neurotransmitter diffuses across the cleft and activates receptors on the postsynapticand activates receptors on the postsynaptic membrane which cause changes on the restingmembrane which cause changes on the resting potential by altering the functioning of ionpotential by altering the functioning of ion channels.channels. 25. ProteinsProteins Ion pumps, ion channels, etc., are largeIon pumps, ion channels, etc., are large molecules of protein.molecules of protein. Proteins are long strings of amino acids that canProteins are long strings of amino acids that can fold into many three dimensional shapes. Thefold into many three dimensional shapes. The same protein can have different configurations,same protein can have different configurations, i.e., they can change shape.i.e., they can change shape. Receptors are protein molecules that changeReceptors are protein molecules that change shape (are activated) by neurotransmittershape (are activated) by neurotransmitter molecules with a particular shape.molecules with a particular shape. 26. ReceptorsReceptors Receptor sites can beReceptor sites can be part of an ion channelpart of an ion channel and when theand when the receptor site isreceptor site is occupied by aoccupied by a neurotransmitter, theneurotransmitter, the ion channel opension channel opens 27. Post synaptic potentialPost synaptic potential The change in the resting potential caused byThe change in the resting potential caused by the activation of a receptor site is called the postthe activation of a receptor site is called the post synaptic potential (PSP).synaptic potential (PSP). IPSP when the change causesIPSP when the change causes hyperpolarization or makes the cell harder tohyperpolarization or makes the cell harder to fire, this is called an inhibitory post synapticfire, this is called an inhibitory post synaptic potential.potential. EPSP when the change causes depolarization,EPSP when the change causes depolarization, this is called an excitatory post synapticthis is called an excitatory post synaptic potential.potential. 28. Post synaptic potentialPost synaptic potential The excitation and inhibition caused by allThe excitation and inhibition caused by all the active synapses on the dendrites andthe active synapses on the dendrites and cell body are summed and the net effectcell body are summed and the net effect is reflected in the rate at which the axonis reflected in the rate at which the axon hillock generates action potentials