Nerves and Muscle Physiology PDF

(NERVES AND MUSCLE) PHYSIOLOGY BY Dr Onaadepo.O 1  ACTION POTENTIAL Change in the membrane potential from resting value to its peak and back again to the resting value They are especially prominent in nerves and muscles They also occur in othe...

(NERVES AND MUSCLE) PHYSIOLOGY BY Dr Onaadepo.O 1  ACTION POTENTIAL Change in the membrane potential from resting value to its peak and back again to the resting value They are especially prominent in nerves and muscles They also occur in other excitable animal cells It can be measured by a cathode ray oscilloscope which was invented by Gasser and Erlanger 2  ACTION POTENTIAL(AP) Generation of AP When a threshold stimulus(adequate in strength) is applied to a nerve, it produces certain potential changes These changes are called ACTION POTENTIAL This is transmitted along the nerve fibre as a self propagated disturbance known as NERVE IMPULSE 3  ACTION POTENTIAL Phases of Action potential and their ionic basis 1. Resting state- Stimulus artifact 2. Latent period 3. Depolarization 4. Repolarization 5. After-depolarization 6. After- hyperpolarization 4  ACTION POTENTIAL Stages of Action potential In a cell at resting stage, threshold stimulus causes depolarization which is initially slow but rate increases after an initial 15mV Point at which the rate increases is called the firing level Once the firing level is reached the potential rises rapidly Reaches the zero potential and overshoots it to approximately + 35 5  ACTION POTENTIAL It then reverses and falls rapidly towards the resting level- repolarization Towards the end of repolarization, the rate of repolarization decreases and the tracing approaches the resting level 6  ACTION POTENTIAL Sharp rise and the rapid fall of the MP are the spike potential of the axon The slower fall towards the end of the process is the after- depolarization 7  ACTION POTENTIAL Usually after repolarization, the potential of the membrane overshoots the starting point The inside becomes more negative than it was originally This is called after- hyperpolarization 8  Phases of Action potential and their ionic basis 9  ACTION POTENTIAL Resting level This the cell in an unexcited state, the inside is negative relative to the outside Stimulus artifact Current leakage from the stimulating electrode to the recording electrode 10  ACTION POTENTIAL Latent period Time taken by the impulse to reach the recording electrode 11  ACTION POTENTIAL Depolarization Due to sudden increase in the permeability of the cell membrane There is loss of normal resting polarized state of the membrane There is increased sodium influx The cell become increasingly more positive with the potential rising in positive direction 12  ACTION POTENTIAL Repolarization Restoration of normal polarized state of the membrane It is a fall in the negative direction from +35 to - 70mV It produces the descending limb It is as result of closure of sodium gates and opening of potassium gates 13  ACTION POTENTIAL After-depolarization Due to slow return of potassium to the closed state 14  ACTION POTENTIAL After-hyperpolarization Due to late closure of the potassium channels more potassium leave the cell than at the resting value 15  ACTION POTENTIAL After the action potential ends, The resting sodium and potassium ionic gradient across the cell are restored by the action of sodium- potassium pump and the ongoing potassium leak channel 16  ACTION POTENTIAL ION CHANNELS Channels or little pores are present in the cell membrane that allow the passage of ions especially sodium and potassium These channels are controlled by the voltage across the cell membrane 17  ACTION POTENTIAL SODIUM CHANNELS Each channel has two gates(doors) One near the outside of the channel(activation gate) The other near the inside of the channel(inactivation gate) The channel is referred to as voltage gated sodium channel 18  ACTION POTENTIAL SODIUM CHANNELS At rest, inactivation gate is opened and does not constitute a barrier to the entry of sodium but activation gate is closed When a stimulus is applied to the cell membrane and the negativity inside the cell is reduced, the activation gate flips open and more sodium rushes rapidly into the cell 19  ACTION POTENTIAL SODIUM CHANNELS When the activation gate has remained opened for few seconds and a lot of sodium has rushed into the cell, the inactivation gate closes to prevent further influx of sodium ions 20  ACTION POTENTIAL POTASSIUM CHANNEL Potassium voltage gated channels are also present on the cell membrane At rest, potassium gates is closed and potassium ions are prevented from passing through to the exterior The voltage change that causes the sodium channels to open also opens the potassium channel 21  ACTION POTENTIAL POTASSIUM CHANNEL Potassium channel are however slow in opening They become opened just at the same time that the sodium channels are beginning to become inactivated and are closing The decrease in the sodium entry into the cell and simultaneous increase in potassium exit from the cell greatly speeds up the repolarization process 22  ACTION POTENTIAL POTASSIUM CHANNEL Although after a while, there is delay in the closing of the potassium channel which is the cause of after-hyperpolarization Excess potassium ions diffuse out of the cell leaving an extra deficit of positive ions inside of the cell The inside becomes more negative than before onset of Action potential 23  ACTION POTENTIAL FACTORS THAT DETERMINE EFFECTIVENESS OF A STIMULUS 1. Intensity (strength) sub threshold stimuli produce on local responses that cannot initiate action potential 2. Rate of increase in the intensity of stimuli- when a threshold stimulating current is used to stimulate a nerve, response depends on the rate of such increase If the intensity is increased slowly, the nerve will not respond because of adaptation A rapid increase in the currents intensity will produce a response 24  ACTION POTENTIAL 3. DURATION OF STIMULUS There is duration of time needed to produce a response The relationship between the intensity of a stimulating current and the duration of its flow necessary to set up an impulse is shown in a STRENGTH- DURATION CURVE 25  ACTION POTENTIAL STRENGTH DURATION CURVE Current strength is plotted against the duration of flow required to give a response 26  ACTION POTENTIAL FROM THE CURVE The stronger the current, the shorter the time needed for production of an impulse There is a minimal duration of time needed for excitation below which no excitation occurs whatever may be the strength of the current 27  ACTION POTENTIAL The minimum strength of a galvanic current that can set up an impulse is called rheobase Below rheobase ,no excitation occurs whatever may be the duration of application 28  ACTION POTENTIAL Significance of the Rheobase Usually around the 1 ms mark on the strength- duration curve, the curve flattens out at the Rheobase, In other words, for longer stimulus durations, the minimal voltage required to bring the nerve to threshold will be the Rheobase. 29  ACTION POTENTIAL The time needed for excitation when using the rheobase is called the utilization time 30  ACTION POTENTIAL Chronaxie This is duration of current flow needed for excitation when using current equal to twice the rheobase 31  ACTION POTENTIAL Significance of the Chronaxie Given that two nerves have the same Rheobase, the Chronaxie (the stimulus duration corresponding to twice the rheobase) can give an indication/measure of their relative excitabilities. In the strength-duration curve to the right, nerve B is the more excitable. The shorter the chronaxie, the greater the excitability and vice versa 32  NERVE IMPULSE CONDUCTION The physiochemical changes produced by various stimuli in the nerve is called nerve impulse i.e , the transmission of depolarization process along a nerve fibre Such impulse is actively and rapidly conducted along the nerve fibres 33  NERVE IMPULSE CONDUCTION MECHANISM OF NERVE IMPULSE CONDUCTION Action potential elicited at any point on an excitable membrane usually excites adjacent portion of the membrane resulting in propagation of action potential along the membrane It occurs in both my myelinated and non myelinated nerves 34  NERVE IMPULSE CONDUCTION In a myelinated nerve fibre Impulses are propagated along nerve fibre by a special mechanism called saltatory conduction 35  NERVE IMPULSE CONDUCTION In non myelinated nerve Positive charges inside the nerve fibre at the point of depolarization flow along the membrane of the nerve These positive charges increase the voltage for a distance of 1-3 millimeters inside large fibres to above threshold for initiating an action potential 36  NERVE IMPULSE CONDUCTION Therefore the sodium channel in this new area immediately gets activated and depolarization is initiated And action potential is generated 37  NERVE IMPULSE CONDUCTION Note The speed of conduction along axons depend on their diameter, the larger the diameter the faster the conduction velocity 38  REFRACTORY PERIOD During propagation of action potential/nerve impulse Excitability of a nerve fibre passes through the following phases 1. Absolute refractory period 2. Relative refractory period 39  REFRACTORY PERIOD Absolute refractory period Period during which the nerve is completely unexcitable, Thus no stimulus can excite it whatever its strength It corresponds to the ascending limb of the AP from the firing level ,to overshoot and upper part of the descending limb (until RP is about 1/3 complete) 40  REFRACTORY PERIOD Relative refractory period Period in which nerve excitability is partially recovered Thus stronger stimulus than normal are required for excitation It corresponds to the remaining part of the descending limb of the AP till the start of another depolarization 41  Factors that can affect excitability of Nerves 1. Temperature- cooling decreases nerve excitability while warming increases 2. Pressure- mechanical pressure on a nerve reduces excitability 3. Blood supply- nerve excitability is decreased in Ischemia 4. Oxygen supply- oxygen lack decreases excitability 5. Ph- alkalinity increases and acidity decreases excitability 6. Electrolytes, Increased with low calcium and hydrogen ions , decreased with high potassium ions 42 Synapse Junction between two neurons. It is not an anatomical continuation, but only a physiological continuity between two nerve cells. Importance of Synapses in the Nervous System 1. Synapses act as unidirectional valves in the nervous pathways i.e. they allow the follow of impulses from the pre-synaptic to the post-synaptic neurons only. This ensures the flow of impulses in the nervous pathways in the forward (orthodromic) direction only. Any impulse that travels along a neuron in the wrong (antidromic) direction cannot be transmitted to the next neuron because it dies off at the first set of synapses it meets. 2. Synapses are also sites in the nervous pathways at which transmission of impulses can be most easily influenced. At the synapse, transmission of impulses can be potentiated, accelerated, inhibited, slowed down or blocked by physiological, pathological or pharmacological influences. 43 Presynaptic Neuron The neuron which conducts impulses to the synapse Postsynaptic Neuron The neuron which conducts impulses away from the synapse Synapse knobs of the presynaptic neuron contain vesicles (synaptic vesicles) which contain the chemical transmitter of the neuron. 44 CLASSIFICATION OF SYNAPSE Synapse is classified by two methods: A. Anatomical classification\ 1.Axoaxonic synapse 2.Axodendritic synapse 3.Axosomatic synapse B. Physiological/Functional classification. 1. Chemical Synapses 2. Electrical synapses 3. Conjoint synapses 45 Anatomical Classification Usually synapse is formed by axon of one neuron ending on the cell body, dendrite or axon of the next neuron. Depending upon ending of axon, synapse is classified into three types: 1. Axoaxonic synapse : Is one in which axon of one neuron terminates on axon of another neuron 2. Axodendritic synapse : Is one in which the axon of one neuron terminates on dendrite of another neuron 3. Axosomatic synapse: Is one in which axon of one neuron ends on soma (cell body) of another neuron Anatomical synapses 46 Physiological/ Functional Classification This type of classification of synapses is on the basis of mode of impulse transmission. 1. Electrical synapse There are gap junctions between the pre-synaptic and postsynaptic membranes which allow the transmission of the depolarization wave (current) directly from the pre- synaptic to the postsynaptic membrane Hence, the action potential reaching the terminal portion of presynaptic neuron directly enters the postsynaptic neuron. Important feature of electrical synapse: a) Synaptic delay is very less because of the direct flow of current. b) Impulse is transmitted in either direction through the electrical synapse. Electrical synapse c) This type of impulse transmission occurs in some tissues like the cardiac muscle fibers, smooth muscle fibers of intestine and the epithelial cells of lens in the eye. 47 2. Chemical synapse. Junction between a nerve fiber and a muscle fiber or between two nerve fibers, through which the signals are transmitted by the release of chemical transmitter (neurotransmitters). Here, there is no continuity between the two neurons because of the presence of a space called synaptic cleft between the two neurons. Action potential reaching the presynaptic terminal causes release of neurotransmitter substance from the vesicles of this terminal. Neurotransmitter reaches the postsynaptic neuron through synaptic cleft and causes the production of potential change. 48 Note: Chemical synapses are the major types of synapses found in the human nervous system 3. Conjoint synapses: Here transmission of impulses occurs by both mechanisms; electrical and chemical. Note: The electrical and conjoint synapses are not usually common in the human body. They are found in some fishes and invertebrates. 49 Properties of synapse 1. One way conduction the impulses are transmitted only in one direction in synapse, i.e. from presynaptic neuron to postsynaptic neuron 2. Synaptic delay Short delay that occurs during the transmission of impulses through the synapse. It is due to the time taken for: i. Release of neurotransmitter ii. Passage of neurotransmitter from axon terminal to postsynaptic membrane iii. Action of the neurotransmitter to open the ionic channels in postsynaptic membrane. Normal duration of synaptic delay is 0.3 to 0.5 millisecond. Synaptic delay is one of the causes for reaction time of reflex activity. 50 3. Fatigue During continuous muscular activity, synapse becomes the seat of fatigue. Fatigue at synapse is due to the depletion of neurotransmitter substance, acetylcholine. Depletion of acetylcholine occurs because of two factors: i. Soon after the action, acetylcholine is destroyed by acetylcholinesterase ii. Due to continuous action, new acetylcholine is not synthesized. 51 4. Summation Fusion of effects or progressive increase in the excitatory postsynaptic potential in post synaptic neuron when many presynaptic excitatory terminals are stimulated simultaneously or when single presynaptic terminal is stimulated repeatedly. Increased excitatory postsynaptic potential (EPSP) triggers the axon potential in the initial segment of axon of postsynaptic neuron Summation is of two types a) Spatial Summation a) Occurs when many presynaptic terminals are stimulated simultaneously b) Temporal Summation Occurs when one presynaptic terminal is stimulated repeatedly. Thus, both spatial summation and temporal Spatial and temporal summation play an important role in facilitation of summation response. 52 5. Electrical property Electrical properties of the synapse are the excitatory post synaptic potential (EPSP) and inhibitory post synaptic potential (IPSP). Convergence and Divergence „Convergence Process by which many presynaptic neurons terminate on a single postsynaptic neuron. „Divergence Process by which one presynaptic neuron terminates on many postsynaptic neurons Convergence and divergence 53 Functions of synapse Main function of the synapse is to transmit the impulses, i.e. action potential from one neuron to another. However, some of the synapses inhibit these impulses so that impulses are not transmitted to the postsynaptic neuron. On the basis of functions, synapses are divided into two types: 1. Excitatory synapses, which transmit the impulses (excitatory function) 2. Inhibitory synapses, which inhibit the transmission of impulses (inhibitory function). 54 1. Excitatory function Excitatory Postsynaptic Potential (EPSP) EPSP is the non propagated electrical potential that develops during the process of synaptic transmission. When the action potential reaches the presynaptic axon terminal, voltage-gated calcium channels at the presynaptic membrane are opened, so that the calcium ions enter the axon terminal from ECF causing the release of neurotransmitter (acetylcholine) substance from the vesicles by means of exocytosis. Neurotransmitter (acetylcholine) which is excitatory in function passes through synaptic cleft and binds with the receptor protein present in postsynaptic membrane to form neurotransmitter - receptor complex. Neurotransmitter-receptor complex causes production of a non propagated EPSP. 55 Sequence of events during synaptic transmission. Ach = Acetylcholine, ECF = Extracellular fluid, EPSP = Excitatory postsynaptic potential 56 Mechanism of Development of EPSP Neurotransmitter receptor complex causes opening of ligand gated sodium channels. Now, the sodium ions from ECF enter the cell body of postsynaptic neuron. Influx of sodium ions alters the resting membrane potential and mild depolarization develops – called EPSP. It is a local potential (response) in the synapse. 57 Properties of EPSP EPSP is confined only to the synapse. It is a graded potential. It is similar to receptor potential and endplate potential. EPSP has two properties: 1. It is non propagated 2. It does not obey all or none law. Significance of EPSP 1. EPSP is not transmitted into the axon of postsynaptic neuron. However, it causes development of action potential in the axon. 2. When EPSP is strong enough, it causes the opening of voltage gated sodium channels in the initial segment of axon. Now, due to the entrance of sodium ions, the depolarization occurs in the initial segment of axon and thus, the action potential develops. From here, the action potential spreads to other segment of the axon. 58 2. Inhibitory function Inhibition of synaptic transmission may be classified into : a) Postsynaptic or direct inhibition Type of synaptic inhibition that occurs due to the release of an inhibitory neurotransmitter (gammaaminobutyric acid (GABA), dopamine and glycine) from presynaptic terminal instead of an excitatory neurotransmitter substance. b) Presynaptic or Indirect Inhibition Occurs due to the failure of presynaptic axon terminal to release Sequence of events during postsynaptic sufficient quantity of excitatory inhibition. GABA = Gammaaminobutyric neurotransmitter substance. acid, ECF = Extracellular fluid, IPSP = Inhibitory postsynaptic potential 59  ANY QUESTION? 60