Nerve. (2) Duration of the stimulus A certain period can give response. The Strength - Duration Curve

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1 Nerve Neuron (nerve cell) is the structural unit of nervous system. Nerve is formed of large numbers of nerve fibers. Types of nerve fibers Myelinated nerve fibers Covered by myelin sheath interrupted at nodes of Ranvier Somatic afferent, efferent fibers & autonomic preganglionic fibers Non-myelinated nerve fiber Not covered by myelin sheath (but surrounded by Schwann cells) Postganglionic autonomic fibers & other nerve fibers < 1µ in diameter Characters of nerve fibers: 1- Excitability 2- Conductivity Excitability : ability of living tissues to respond to stimuli. The most excitable tissues in the body are nerves & muscles. Stimuli are changes in the environment that excite an organism Types of stimuli electrical (preferred & used), mechanical, chemical & thermal. Factors affecting the effectiveness of electric stimulus: (1) Strength (intensity) of the stimulus Certain amplitude can excite the nerve (2) Duration of the stimulus A certain period can give response. (3) Rate of rise stimulus intensity Rapid of stimulus intensity: gives response. Slow of stimulus intensity: accommodation no response The Strength - Duration Curve The stronger the stimulus, the shorter its duration needed to excite the nerve within limits. Stimuli of very short duration will not excite the nerve whatever the intensity. Rheobase (threshold stimulus): The minimal current that excite the nerve. Utilization time: time needed by rheobase to excite the nerve Subthreshold (subminimal) stimuli: cause localized changes in the nerve (local response or local excitatory state) Chronaxie: time needed by current twice the rheobase intensity It is a common measure of excitability. If excitability of nerve is high, the chronaxie is shortened. chronaxie of nerve fibers < chronaxie of muscle fibers Membrane potential Membrane potential electrical potential (voltage difference) between the inside & outside the cell (i.e. across the membrane). It is responsible for excitability. Measuring the membrane potential CRO to measure very small & very rapid electric changes Forms of membrane potential (1) Resting membrane potential: during rest. (2) Action potential: on stimulation of the nerve by threshold stimulus. (3) Localized (electrotonic) potentials: on stimulation of the nerve by subthreshold stimulus (1)

2 Resting Membrane Potential (R.M.P.) (polarized state) Definition electrical potential (voltage difference) between inside & outside membrane surfaces under resting conditions. The inside is ( ve) : the outside of the membrane R.M.P. Causes of R.M.P. (1) Selective permeability of the membrane (for Na + & K + ). (2) Na + K + pump. (1) Selective permeability of the membrane: At rest Na + Cl HCO 3 Inward rectifying times K + channels ++ K + ++ proteins 3 PO 4 outside inside 4 K Na + outside conc. electrical conc. electrical At equilibrium gradient = gradient gradient = gradient 140 K + 14 Na + inside (2) Na + K + pump: In large nerve fibers & large skeletal muscles is 90mV. In medium sized neurons is 70 mv. In non excitable cells (RBC s & epithelial cells) is 20 to 40 mv. The RMP is ( ) means the inside is ve in relation to outside. Na + - K + pump is electrogenic (helps to keep the membrane potential). Calculation of R.M.P. 1- Nernst equation: (1) Contribution of K + diffusion potential Conc. inside E (millivolt) = ± 61 log Conc. outside [K + ] in 140 EK + = 61 mv log = 61 mv log = 61 mv 1.54 = 94 mv. [K + ] out 4 (2) Contribution of Na + diffusion potential [Na + ] in 14 ENa + = 61 mv log = 61 mv log = 61 mv 1 = 61 mv [Na + ] out Goldman equation (more accurate) (C Na + i x P Na + ) + (C K + i x P K + ) + (C Cl o x P Cl ) E (millivolt) = 61 log (C Na + o x P Na + ) + (C K + o x P K + ) + (C Cl i x P Cl ) The calculated R.M.P. by diffusion of ions is 86 mv. (95% of R.M.P) Contribution of Na + K + pump: 4 mv (5 % of R.M.P.) The net membrane potential of all these factors together at the same time = 90 mv (the RMP) Diffusion is the main factor which determines R.M.P. ( 86 mv) K + diffusion causes almost all of this R.M.P (due to high permeability of the membrane to it) (2)

3 Action potential Definition Rapid changes in the membrane potential following stimulation of the nerve by threshold stimulus. Phases & shape of AP Stimulus artifact: Latent period: depends on: Distance between site of stimulus & recording electrode. Velocity of nerve impulse (speed of conduction) Depolarization phase Components of AP Repolarization phase Hyperpolarization phase Spike: sharp rise & rapid fall of M.P.(2 msec) Hyperpolarization: (35 40 msec) (1) Depolarization phase (2) Repolarization phase Rapid phase: the 1st 70% of repolarization Slow depolarization: the 1st 25 mv depolarization from ( 90 to 65 mv) The firing level: ( 65 mv),the level at which the rate of depolarization increases. Rapid depolarization: The M.P. rapidly reaches the isopotential "zero potential" & then overshoots to (+35 mv) i.e. reversal of polarity So: the magnitude of A.P. is 125 mv. ( ) Determined by: Voltage gated Na + channels Voltage gated K + channels Ionic basis of AP Slow phase: the remaining 30% of repolarization, till the R.M.P. is reached (3) Hyperpolarization phase The M.P. overshoots the (R.M.P.) in the hyperpolarization direction to form small but prolonged hyperpolarization. Depolarization: (Na + entry) Repolarization: (K + exit) (1) During depolarization (2) During repolarization The initial depolarization: stimulus open some of the Na + channels Na + entry (by electro-conc. gradient) The flow of Na + into the fiber more depolarization more Na + channels open & so on (+ve feedback) Till all Na + channels are opened (activated). At the firing level ( 65 mv) rapid depolarization (ascending limb of the spike) During overshoot: reversal of M.P. inactivation of Na + channels limits Na + entry (3) Inactivation of Na + channels stops Na + entry Activation of K + channels K + exit (by electro-conc. gradient) The opening of gates of K + channels is slower & more prolonged than opening of Na + (3) During hyperpolarization caused by the slow closing of K + channels So: K + conductance (at the end of AP) > during the resting state hyperpolarization. Role of inward rectifier K + channels: drive membrane potential from hyperpolarization RMP (They move K + inward the nerve only in cases of hyperpolarization) Re-establishing of Na + & K + gradients after AP: (by Na + K + pump)

4 All or none law The action potential obeys all or none law AP is either generated & conducted maximally or not produced at all Regardless of the intensity of the stimulus at or above threshold (provided that other experimental conditions remain constant) Excitability changes during the AP During the initial depolarization up to the firing level, the nerve excitability is increased During the remaining part of action potential; the nerve is refractory to restimulation: (a) Absolute refractory period (ARP) It is the period of time during which a second AP cannot occur even with a very strong stimulus. It extends from the firing level till the end of the early part of repolarization. Cause: The Na + channels are inactivated: inner gates are closed & can't be opened for sometime. Function of refractory period: To protect the nerve from extremely rapid repetitive stimulation, which would compromise its function Effect of sub-threshold stimuli (b) Relative refractory period (RRP) It is the period of time during which stronger than normal stimuli can produce AP It extends from the end of ARP till membrane potential returns to its resting state Cause: (1) Some of Na + channels return to their resting state & can be activated (2) K + channels are opened widely causing hyperpolarization (Electrotonic potentials) Electrotonic potentials (Local response) (a) Catelectrotonus Occurs at the region of cathode. A state of partial depolarization (passive) (< 7mv) due to addition of ( ve) charges by the cathode at the outer surface of the nerve fiber The excitability is *; the threshold is & M.P. moves closer to the firing level (b) Anelectrotonus Occurs at the region of anode. A state of hyperpolarization due to addition of (+ve) charges by the anode at the outer surface of the nerve fiber The excitability is *; the threshold is & M.P. moves away from the firing level Local response (local excitatory state) Action potential Local response Stimulus: threshold or suprathreshold. Stimulus: subthreshold. A state of complete depolarization, reversal A state of partial depolarization (below the firing of polarity then repolarization level) followed by rapid repolarization to RMP Propagated Non-propagated (fades away within 1 2mm) Not graded i.e. the magnitude of AP does not Graded i.e. the magnitude of local response change by changing the intensity of stimulus by increasing the intensity of stimulus Not summated i.e. the magnitude of AP Summated i.e. the magnitude of local response does not by addition of another stimuli by addition of another subthreshold stimuli reach the firing level & produce new AP. Obeys all or none law. Does not obey all or none law. Nerve excitability is * up to the firing level, Nerve excitability is * as the M.P. moves but the remaining part of AP is refractory to towards the firing level. restimulation (ARP) & (RRP). Has no refractory period N.B. * Excitability changes during nerve stimulation (4)

5 Factors affecting excitability of the nerve Role of Na + (1) Factors that excitability (2) Factors that excitability Conditions that nerve permeability to Na + Conditions that nerve permeability to Na + Veratrine. Local anesthetics e.g. cocaine Low Ca ++ conc. in the E.C.F. High Ca ++ conc. in the E.C.F. Na + in the E.C.F. AP magnitude but has little effect on R.M.P. Block of Na + channels by tetrodotoxin (TTX) nerve excitability & no AP could be elicited Role of K + R.M.P. is primarily dependant on conc. gradient of K + Repolarization is caused by K + exit. (1) Factors that excitability (2) Factors that excitability extracellular K + conc. Makes equilibrium potential for K + more +ve membrane depolarization extracellular K + conc.: makes equilibrium potential for K + more ve hyperpolarization. This occurs in a hereditary disease (familial periodic paralysis) marked nerve excitability no nerve impulses produced muscle paralysis. It is treated by I.V. K +. Block of K + channels by tetraethylammonium (TEA) prolonged AP due to prolonged repolarization but hyperpolarization is absent Role of Na + K + pump Re-establishing Na + & K + gradients after AP Block of Na + K + pump affects R.M.P. & genesis of AP All factors that the excitability are called membrane stabilizers Accommodation of nerve fibers Gradual slow in intensity of a subthreshold stimulus to threshold level no response It is due to: the slow activation (opening) of Na + channels slow entry of Na + is balanced by: Inactivation (closure) of Na + channels. Opening of K + channels. Monophasic & Biphasic AP Monophasic AP Recorded if the 2 electrodes are placed on 1 point of the nerve (one inside & one outside) Biphasic AP Recorded if the 2 electrodes are placed on 2 points of the outer surface of the nerve fiber Compound action potential It has many peaks on its descending limb (compound). Because: the nerve fibers vary in their: 1. Stimulation threshold. 2. Site (distance) from stimulating electrodes. 3. Speed of conduction according to their thickness. Compound AP is graded 1- Subthreshold stimuli no response. 2- stimulus strength to threshold a small AP 3- More the intensity of stimulation AP amplitude, up to a maximum (maximal stimulation) 4- More the intensity of stimulation "Supramaximal stimuli" will not the amplitude of AP. (5)

6 Conduction (propagation) of action potential Propagation in unmyelinated nerve fibers: The stimulated area: reversal of polarity. The adjacent area: polarized (resting). (a) So: potential difference is generated between these 2 areas & a local circuit of current flow occurs between the depolarized area of the membrane & the adjacent resting areas. (b) The adjacent areas become depolarized to threshold action potential is generated, while the active segment returns to its resting level. (c) The new action potential spreads passively & the process is repeated. The speed of propagation α nerve fiber diameter Propagation in myelinated nerve fibers Saltatory conduction The same in principle as in unmyelinated fibers The action potentials are generated only at the nodes of Ranvier AP spreads from one node to the adjacent one (+ve) charges jump from the resting node to the activated neighboring node Importance of saltatory conduction: 1- velocity of conduction of nerve impulse up to 50 folds. 2- Conserves the energy for the axon to be used only at nodes of Ranvier The spread of propagation α fiber diameter & internodal distance. Orthodromic & Antidromic conduction Orthodromic conduction: in normal direction (receptors afferents terminations) Antidromic conduction: in the opposite direction along the nerve fiber Nerve fiber types A fibers B Fibers C Fibers (1) Thickness 2 20 microns 1 5 microns < 1 micron (2) Velocity m/sec 5 15 m/sec m/sec (3) Spike duration 0.5 msec 1 msec 2 msec (4) Susceptibility More to pressure More to hypoxia More to local (5) Example & hypoxia. Myelinated somatic nerves Subdivided into: α, β, γ, δ During rest Energy is needed to maintain (RMP). Energy for Na + K + pump is derived from the breakdown of ATP. Thus, the nerve has a resting heat while inactive & pressure Myelinated preganglionic autonomic nerves Metabolism of the nerve anesthesia Unmyelinated postganglionic autonomic nerves During activity Na + pump prevents Na + conc. inside the nerve Na + pump activity α (Na + conc. inside the nerve) 3 During activity heat production by the nerve is It is of 2 types: ratio a- Initial heat: (during AP) 1 : b- Recovery heat: (after AP) 30 (6)