1. PHYSIOLOGY OF THE NERVE

2. Typical nerve cell has cell body (soma) with 5-7 short projections (dendrites) and a longer fibrous axon. The axon ends in a number of synaptic knobs (terminal buttons) which stores the neurotransmitter. Axons of some nerve fibers have a myelin sheath, (a protein-lipid insulator formed by Schwann cell wrapping around the axon.) The sheath envelops the axon except at its ends and periodic constrictions of 1 mm distance (node of Ranvier), these are called myelinated nerve fibers soma nucleus dendrites Axon terminals Myelin sheath Nod of Ranvier Presynaptic terminals Schwann cell nucleus

3. Genesis Of Resting Membrane Potential (RMP) RMP is an Electrical potential exists across the membranes of all body cells with a negative charge inside the cell relative to the positive charge outside.it due to 1-passive diffusion of Na, and K, ions through leak channels (passive channels, are always open, allowing the passage of sodium ions (Na+) and k but more permeable to k)this create (-86 mv)

4. 2-Na-K pump: this is an electrogenic pump because more positive charges are pumped to the outside than to the inside leaving a net deficit of positive ions on the inside. This will add (-4 mv) making a total of (-90 mv) This -90 mv is the RMP for large neuron

6. NERVE ACTION POTENTIAL (AP) Nerve signal (impulse) is transmitted by action potential. sudden change from the normal negative resting potential inside the cell to a positive potential (depolarization) followed by rapid return back to the negative potential(repolarization). Action potential moves along the nerve fiber to its end in a constant rate and amplitude

7. STAGES OF ACTION POTENTIAL 1. Resting stage: The membrane is said to be “polarized” –90 millivolts. 2. Depolarization: a. increased Na permeability by opening voltage-gated Na channels. inside becomes positive. And the membrane potential to “overshoot” beyond the zero 3. Repolarization: a. closure of voltage-gated Na channels. b. increasd K permeability by opening voltage-gated K channels K move out c. inside cell returns back to negative. Action potential lasts for 1 millisecond in large myelinated nerve fiber. Resting stage Depolarization Repolarization Over shoot

9. Stimulus For Nerve and Muscle Excitation 1.Chemical 2.Mechanical pressure. 3. Electrical current. all above factors increases membrane permeability to Na (leak channels) shifting the membrane potential toward the firing level(open voltage gated Na channels) producing an AP

10. CATHODE-RAY OSCILLOSCOPE (CRO) An electrical instrument used to record very small electrical events (mv) which occurs very rapidly (ms) in the living tissues. CRO has two electrodes applied to the nerve, a stimulating electrode and a recording one

11. ACTION POTENTIAL AS RECORDED BY CRO 1. latent period: the time taken by an impulse to travel from the stimulating electrode to the recording electrode. From the duration of the latent period the velocity of nerve conduction can be calculated. 2. Depolarization: slow at first but after initial 15 mv of depolarization the rate increases sharply(firing level) due to sudden opening of fast Na channels. 3. Repolarization: this stage starts by closure of fast Na channels and opening of K channels retuning membrane potential back to the polarized state. 4. After depolarization: when the repolarization is 70% completed the rate is decreased due to built up of large amounts of K outside the cell which resist K outflow. 5. After hyperpolarization: when membrane potential reaches the resting level, it becomes somewhat more negative than normal because: 1 2 3 4 5 6

12. REFRACTORY PERIOD Refractory period : 1. Absolute refractory period: the period from firing level until repolarization is about half completed. During Absolute refractory period, a second stimulus will not produce a second action potential 2. Relative refractory period: from end of absolute refractory period. Another action potential can be produced, but only if the stimulus is very strong

13. With increasing stimulus strength, subsequent action potentials occur earlier during the relative refractory period of the preceding action potentials.

14. Threshold stimulus The minimum intensity of stimulus that will just produce a response (AP). It varies according to the type of axon

15. At the level of single nerve axon, any stimulus with subthreshold intensity will not produce an AP. Again, increasing the stimulus intensity above threshold level will produce no change in response, thus the AP of a single nerve axon obey the "all- or- none law“ ( all-or-nothing principle)

16. PROPERTIES OF MIXED NERVES Each peripheral nerve consists of a number of neurons bound together by fibrous sheath 1. Different neurons have different thresholds: Subthreshold stimulus produce no response. When threshold stimulus is applied, some neurons with low threshold intensity will respond first producing an AP.

17. As the stimulus intensity is increased (submaximal stimulus), more and more neurons will be brought about into action (recruitment) producing larger AP. The stimulus which excites all neurons is called maximal stimulus. After that, increasing stimulus intensity (supramaximal stimulus) will produce no change in response, therefore mixed nerves don't obey all or none law. 2. Different neurons have different speed of conduction giving rise to compound AP on recording

18. SUMMATION OF NERVE IMPULSES Nerve impulses obey all- or- none law, however stronger nerve signals can be obtained by two means: 1. Spatial summation: many fibers discharge impulses at the same time. 2. Temporal summation: the same fiber discharge impulses rapidly and repeatedly

19. PROPAGATION OF AP Nerve cell membranes are polarized at rest with outside positive. When stimulus of enough strength is applied on axon, an AP will be generated at the site of stimulation causing polarity to be reversed (inside becomes positive). Positive charges then move from the adjacent part of membrane to the area of negativity creating a local circuit of current flow between the depolarized area and the adjacent resting area of the membrane This spontaneous sequence of events will move along the unmyelinated axon in both directions to its end

20. In myelinated axons, AP will jump from one node of Ranvier to another. This type of conduction is called saltatory conduction which is about 50 times faster than the unmyelinated fiber electrical current flows through the surrounding extra-cellular fluid outside the myelin sheath as well as through the axoplasm inside the axon from node to node, exciting successive nodes one after another

23. FACTORS WHICH AFFECT THE CONDUCTION VELOCITY 1-Myelination 2- Axon diameter: in unmyelinated nerve axon, the conduction velocity is directly proportional to the square root of axon diameter while in the myelinated neuron conduction velocity increases directly with axon diameter

24. PLATEAU IN SOME AP In some excitable tissues, repolarization does not occur immediately after depolarization, instead the membrane potential remains near the peak of spike for many milliseconds(plateau), therefore plateau greatly prolongs the period of depolarization. This type of AP is seen mainly in cardiac muscle where it lasts for as long as 0.3 seconds thus prolonging the time for cardiac contraction. Plateau is due to: 1. Opening of slow Ca –Na channels, 2. Delayed opening of voltage-gated K channels. plateau

25. SPONTANEOUS RHYTHMICITY Spontaneous discharge occurs normally in cardiac (heart beating) and smooth muscle (intestinal peristalsis) and many neurons in the CNS (rhythmic control of breathing). Spontaneous repetitive discharge occurs due to Na leak during the resting state. The RMP of such cells is about - 60 to -70 mv which is not enough to keep Na or Ca channels closed so there will be Na or Ca leak to inside the cell making the membrane potential less negative, this will cause more channels to open allowing more Na and Ca inflow then opening more new channels and so on. This regenerative process is repeated until the firing level is reached and another AP is produced. At the end of AP, the membrane repolarizes again but shortly then after a new AP is generated spontaneously.

26. THE EFFECT OF CALCIUM IONS ON NEURON EXCITABILITY A decrease Ca ion concentration in extra cellular fluid (hypocalcemia) leads to increased neuron excitability due to the easily opening the voltage-gated Na channels. it leads to spontaneous discharge in many peripheral nerves causing muscle tetany.

27. Factors Which Inhibit Nerve Exitability 1. Hypercalcemia(high ECF Ca). 2. Hypokalemia (low ECF K) 3. Local anesthesia

28. ORTHODROMIC AND ANTIDROMIC CONDUCTION An axon can conduct in both directions, however in living animals' impulses pass in one direction only from synaptic junction or receptors then along the axon to their termination. Such conduction is called orthodromic while conduction in the opposite direction is called antidromic. Synapse permits conduction in one direction only.