1. ACTION POTENTIAL: Dr. Ayisha Qureshi Assistant Professor MBBS, MPhil

2. DEFINITIONS: Stimulus: A stimulus is an external force or event which when applied to an excitable tissue produces a characteristic response. Subthreshold stimulus: A stimulus which is too weak to produce a response is called a Subthreshold stimulus. Threshold stimulus: The minimum strength of stimulus that can produce excitation is called a Threshold stimulus. Suprathreshold stimulus: Stimuli having strengths higher than threshold stimulus are called Suprathreshold stimuli.

3. REMEMBER: IMPORTANT: Sodium voltage-gated channels: are fast channels & have 2 gates: - An outer Activation gate(closed in resting state) - An Inner Inactivation gate(open in resting state) Potassium channels are slow channels & have only ONE gate. These channels are different from Sodium & Potassium leak channels. The Sodium-Potassium PUMP is present separately.

4. ACTION POTENTIAL:

5. Action Potential: Definition: An Action Potential is a self-propagating wave of electro-negativity that passes along the surface of the axolemma of the nerve fibers.

6. We know that the inside of the nerve membrane is negative with respect to the outside (RMP=—90 mv) When an effective stimulus(threshold or suprathreshold) is applied, the electrical charge on the membrane is reversed: at the active part of the nerve fibre on the outside becomes negative as compared to the corresponding region in the interior. This is called DEPOLARIZATION and forms the Action Potential.

8. PHASES OF AN ACTION POTENTIAL: Phase 1: Depolarization Phase 2: Repolarization Phase 3: Hyperpolarization

13. IONIC BASIS OF AN ACTION POTENTIAL: 1.DEPOLARIZATION: Sodium (Na) Influx 2.REPOLARIZATION: Potassium (K) Efflux 3.HYPERPOLARIZATION: Leakage of excess Potassium (K) ions through the slow closing K channels. 4.RETURN OF THE AP TO THE RMP FROM HYPERPOLARIZATION: Sodium-Potassium Pump

16. DEFINITIONS: LATENT PERIOD: It is the time period between the application of a stimulus and the start of the response (Action Potential). DEPOLARIZATION: When during the transit changes in the action potential, the Potential difference between the inside of the membrane (-90mv) and outside (0mv) decreases it is called depolarization ( the tracing will move upwards in the AP diagram). REPOLARIZATION: A return to the resting membrane potential from either direction (i.e. de- or hyper-polarization) is called repolarization. HYPERPOLARIZATION: When during the transit changes in the action potential, the Potential difference between the inside of the membrane (-90mv) and the outside (0mv) increases it is called Hyperpolarization.

17. PROPAGATION OF AN ACTION POTENTIAL: Conduction of an Action Potential in a Myelinated and an Unmyelinated nerve fibre:

20. Continuous Conduction Occurs in unmyelinated axons. In this situation, the wave of de- and repolarization simply travels from one patch of membrane to the next adjacent patch. APs moved in this fashion along the sarcolemma of a muscle fiber as well. Analogous to dominoes falling.

21. Saltatory conduction in a Myelinated Neuron:

22. Which do you think has a faster rate of AP conduction – myelinated or unmyelinated axons? Answer: Myelinated axon

23. Name the events & ions responsible for: – Depolarization – Repolarization – Hyperpolarization OR Undershoot – Return of the AP from the Overshoot to the RMP

24. PROPERTIES OF A NERVE FIBRE:

25. 1. ALL OR NONE LAW (also called the All or Nothing Law) On application of a stimulus, an excitable membrane either responds with a maximal or full-fledged action potential that spreads along the nerve fiber, or it does not respond with an action potential at all. This property is called the all-or-none law. (This is in direction proportion to the strength of the stimulus applied.) e.g: This is similar to firing a gun. Either the trigger is NOT pulled sufficiently to fire the gun (subthreshold stimulus) OR it is pulled hard enough to fire the gun (threshold is reached). Squeezing the trigger harder does not produce a greater explosion, just as pulling the trigger halfway does not cause the gun to fire halfway.

26. 2a: ABSOLUTE REFRACTORY PERIOD Definition: Once an action potential has been generated, the time period during which even a suprathreshold stimulus will fail to produce a new action potential is called the Absolute Refractory period. During this time the membrane becomes completely refractory (‘stubborn’ or ‘unresponsive’) to any further stimulation. It corresponds to the entire Depolarization phase & most of the Repolarization phase. Due to Absolute refractory period, one AP must be over before another can be initiated at the same site. APs cannot be overlapped or added one on top of another.

27. BASIS OF AN ABSOLUTE REFRACTORY PERIOD: During the depolarization phase of AP, the voltage- gated Sodium channels have still NOT reset to their original position. For the Sodium channels to respond to a stimulus, 2 events are important: 1.Sodium channels be reset to their closed but capable of opening position. i.e: inactivation gates open and activation gates closed. 2.The Resting membrane potential must be re- established.

28. 2b: Relative Refractory Period Definition: Following the absolute refractory period is seen a period of short duration during which a second action potential can be produced, only if the triggering event is a suprathreshold stimulus. This period is called the Relative Refractory Period. It corresponds to the last half of the Repolarization phase.

29. Basis of a Relative Refractory Period: An action potential can be produced by a suprathreshold stimulus because of the following reasons: 1.By the end of the repolarization phase, some Na channels have reset while some K channels are also still open. 2.Thus, a greater than normal triggering event (suprathreshold stimulus) is required to produce an AP.

31. What is the significance of the REFRACTORY PERIOD (both absolute & relative): 1.There is no fusion or summation of the action potentials. This intermittent, ie. Not continuous conduction of nerve impulses is one of the reasons why a nerve fibre can respond to continuous stimulation for hours without getting tired. Thus, it decreases fatigue in a nerve fibre. 2.The Action Potentials are produced separate from each other. So, a new AP is produced in each part of the nerve fibre. This ensures that the AP does not die out as it is conducted along the membrane. 3.Only a certain number of Action Potentials can be produced in a nerve fibre because the interval between any 2 action potentials cannot be shorter than the Absolute Refractory Period. This prevents fatigue of the nerve fibers and sets an upper limit on the maximum numbers of AP that can be produced in a nerve fibre in a given period of time. 4. By the time the original site has recovered from its refractory period and is capable of being restimulated by normal current flow, the action potential has been propagated in the forward direction only and is so far away that it can no longer influence the original site. Thus, the refractory period ensures the one-way propagation of the action potential down the axon away from the initial site of activation.

32. 3. COMPOUND ACTION POTENTIAL:

33. 3. Compound Action Potential is seen in a “nerve trunk” & NOT a nerve fibre: An action potential having more than one peak/spike is called a Compound action potential. CAUSE: A nerve trunk contains many nerve fibres differing widely in their excitability & different speeds of conduction of AP. Multiple peaks are recorded with the AP from fastest conducting nerve fibre first to be recorded followed by the slower ones....

34. MULTIPLE SCLEROSIS:

35. Multiple Sclerosis: Going, Going, Gone….. It is an auto-immune disease in which there is patchy loss of myelin sheath of nerve fibers leading to disruption of nerve impulse conduction. Cause: Antibodies mistakenly attack and destroy Schwann cells, thus also destroying the myelin sheath. Signs & symptoms: Patchy destruction of myelin in the CNS→ slow & abnormal conduction of the nerve impulses in the neurons ↓ 1.Visual disturbances 2.Tingling & numbness 3.Muscle weakness & Fatigue 4.Gradual paralysis 5.Bladder & bowel problems

38. Treatment Debilitating disease but not fatal. The quality of life is affected…. Death may occur when the paralysis reaches the respiratory muscles and the person cannot breathe. No treatment as yet. Only symptomatic treatment.  Immunosuppressive therapy: as autoimmune disease so you try to suppress the immune system to prevent further damage.  Corticosteroids  Alternative therapy: as homeopathy, ayurvedic treatment etc