Nerve and Muscle. Physiology of nerve

Transcription

1 Nerve and Muscle Physiology of nerve

2 The neuron The basic structural unit of the nervous system. Structure: The soma The dendrites: antenna like processes The axon: hillock, terminal buttons

3 Types of nerve fibers a- myelinated nerve fiber: Covered by myelin sheath, protein-lipid layer, secreted by Schwann cells, acts as insulator to ion flow, interrupted at Nodes of Ranvier b- unmyelinated nerve fiber: Less than 1μ, covered only with Schwann cells, as postganglionic fibers

4 Electrical properties of a neuron Electrical properties of nerve & muscle are: 1-There is difference in electrical potential between the inside and outside the membrane 2-Excitability: the ability to respond to any stimulus by generating action potential 3-Conductivity: the ability to propagate action potential from point of generation to resting point

5 Membrane potential; the basis of excitability Def: electrical difference between the inside & outside the cell Causes: selective permeability of the membrane more K+, Mg2+, Ptn, PO4 inside more Na+, Cl-, HCO3-outside Exists in all living cells & it is the basis of excitability Excitability: Def: it is the ability to respond to stimuli (change in the environment) giving a response The most excitable tissues are nerves & muscles Stimuli: +anode - cathode Types: Electrical (preferred), chemical, mechanical, or thermal. Cathode ( more important) & anode

6 Excitability Factors affecting effectiveness of the stimulus: 1- strength: effective stimulus 2- duration: a certain period of time, very short duration can not excite the nerve 3- rate of rise of stimulus intensity: Rapid increase. Active response Slow increase. adaptation

7 Strength Duration Curve Within limits stronger intensity shorter duration Strength: Threshold stimulus (rheobase): it is the minimal amplitude of stimulus that can excite the nerve and produce action potential. Subthreshold stimulus: causes local response (electrotonic) Duration: stimuli of very short duration can not excite the nerve Utilization time: is the time needed by threshold stimulus (Rheobase) to give a response :Chronaxie time needed by a stimulus double the rheobase to excite the nerve, it is a measure of excitability, decrease chronaxie means increase excitability

8 Strength Duration Curve Stimulus amplitude chronaxi e 2R Utilization time duration R

9 Measuring the membrane potential Recording: by 2 micoelectrodes inserting one inside the fiber & the other on the surface & connected to a voltmeter through an amplifier

10 Types of membrane potential Membrane potential has many forms: 1- RMP 2- on stimulation; a) action potential if threshold stimulus b) localized response (electrotonic) if subthreshold stimulus

11 Resting membrane potential (RMP) *definition: It is the difference in electrical potential between the inside and outside the cell membrane under resting conditions with the inside negative to the outside Recording: by 2 micoelectrodes inserting one inside the fiber & the other on the surface & connected to a voltmeter Value:-90 mv large fibers, -70 in medium fibers, -20 in RBCs Causes 1- selective permeability 2- Na-K pump

12 Resting Membrane Potential Selective permeability of the membrane: contributes to -86mv K+, ptn-, Mg2+&PO4- are concentrated inside the cell Na+, Cl-, HCO3- are found in the extracellular fluid During rest the membrane is 100 times more permeable to K+ than to Na+, K+tend to move outward through INWARD RECTFIER K+ channels down their concentration gradient The membrane is impermeable to intracellular Ptn-&other organic ions Accumulation of +ve charges outside & -ve charges in At equilibrium :K+ in to out is 35:1 Na+ in to out is 1-10

13 Potassium equilibrium -90 mv

14 Na-K pump Definition: carrier protein on the cell membrane: 3 binding sites inside for Na+ 2 sites outside for K+ 1 site for ATP Inner part has ATPase activity It is an electrogenic pump Contributes for -4mv and helps to keep RMP

15 Nernest equation E for K = -61 log con inside/ conc outside =- 94 E for Na = -61 log con inside/ conc outside =+ 61 Goldman equation: it considers 1- Na, K and cl concentrations. 2- K permeability is 100 times as that for Na

16 Action Potential Definition: It is the rapid change in membrane potential following stimulation of the nerve by a threshold stimulus. Recording: microelectrodes and oscilloscope.

17 Membrane Permeabilites AP is produced by an increase in Na + permeability. After short delay, increase in K + permeability. Figure 7-14

18 Shape and Phases of Action Potential 1- Stimulus artifact.: small deflection indicates the time of application of stimulus, it is due to leakage of current 2- Latent Period: isoelectrical interval, time for AP to travel from site of stimulation to recording electrode. 3- Ascending limb (depolarization):starts slowly from -90, till firing level-65mv, reaches &overshoots the isopotential, ends at Descending limb:(repolarization): starts rapidly till 70% complete then slows down * Hyperpolarization: in the opposite direction slight & prolonged 5- RMP

19 Shape and Phases of Action Potential 1- Ascending limb (depolarization) Slow..firing level..rapid. 2- Descending limb (repolarization) rapid then slow 3- Hyperpolarization: slight & prolonged 4- RMP mv overshoot depolarization repolarization FL hyperpolarization Latent period time

20 Duration of Action Potential Spike lasts 2msec Hyperpolarization 35-40msec

21 Ionic basis of action potential Depolarization is caused by Na+ inflow Repolarization is caused by K+ outflow Two types of gates: 1- voltage gated Na+ channels; having 2 gates: outer activation gate & inner inactivation gate 2- voltage gated K+ channels; one activation gate When the nerve is stimulated:: a- the outer gate of VG Na+ opens, activating Na+ channel. Na+ inflow b- the inner gate of Na+ channels closes, inactivating Na+ channels stop Na inflow c- K+ gates open, activating K+ channels, K+ outflow

22 The Action Potential A stimulus opens activation gate of some Na + channels depolarizing membrane potential, allowing some Na to enter, causing further depolariztion If threshold potential is reached, all Na + channels open, triggering an action potential.

23 The Action Potential 1-Depolariztaion:occurs in 2 stages: Slow stage: -90 to -65mv: some Na + channels opened, depolarizing membrane potential, allowing some Na to enter, causing further depolarization At -65mv, the firing level or threshold for stimulation, all Na + channels open, triggering an action potential. Rapid stage: -65 to +35: all Na+ channels are opened, Na+ rush into the fiber, causing rapid depolarization

24 The Action Potential Within a fraction of msec, Na + channel inactivation gates close and remained in the closed state for few milliseconds, before returning to the resting state. 2- Repolarization: Inactivation of Na+ channels and activation of K + channels are fully open. Efflux of K + from the cell drops membrane potential back to and below resting potential 3- Hyperpolarization; slow closure of K+ channels

25 The Action Potential The Na+ & K+ gradients after action potential are re-established by Na+/K+ pump Only very minute fraction of Na+ & K+ share in action potential from the total concentration The action potential is an all-or-none response. (provided that all conditions are constant, AP once produced, is of maximum amplitude, constant duration & form, regardless the amplitude of the stimulus, however threshold or above Action potential will not occur unless depolarization reaches the FL (none) Action potential size is independent of the stimulus and once depolarization reaches FL, maximum response is produced, reaches a value of about +35 mv(all)

26 The Action Potential Both gates of Na + channel are closed but K + channels are still open. K + channels finally close and Na + channel inactivation gates open to return to resting state. Continued efflux of K + keeps potential below resting level.

27 Action potential initiation S.I.Z.

28 Action potential termination

29 Action potential in a nerve trunk Nerve trunk is made of many nerve fibers The AP recorded is compound action potential, having many peaks The individual fibers vary in: 1- threshold of stimulation 2-distance from stimulating electrode 3- speed of conduction

30 During depolarization, there is +ve feed back response. Repolarization is due to: 1- inactivation of Na+ channels( must be removed before another AP 2- slower & more prolonged activation of K+ channels Hyperpolarization (undershoot): slow closing of K+ channels, K+ conductance is more than in resting states Role of Inward rectifier K+ channels: Non gated channels Tend to drive the membrane to the RMP Drive K+ inwards only in hyperpolarization Re-establishing Na+ &K+ gradient after AP:role of Na+ /K+ pump All or none law

31 Electrotonic potentials & local response Catelectronus: at cathode/ depolarization less than 7mV/ passive Anelectronus: at anode/ hyperpolarization/ passive Local response (local excitatory state): Stonger cathodal stimuli Slight active response Some Na+ channels open, not enough to reach FL It is graded Does not obey all or none law Non propagated Excitability of the nerve increased Caused by subthreshold stimulus Can be summated & produce AP Has no refractory period

32 Local Response (local excitatory change) Although subthreshold stimuli do not produce AP they produce slight active changes in the membrane that DO NOT PROPAGATE. It is a state of slight depolarization caused by subthreshold cathodal stimulus that opens a few Na channels not enough to produce AP

33 Local Response (local excitatory change) It differs from AP : It does not obey all or non rule Can be graded. Can be summated. It does not propagate.

34 Excitability changes during the action potential Up to FL, excitability increases The remaining part of action potential, the nerve is refractory to stimulation (difficult to be restimulated) Absolute refractory period: Def: the period during which a 2 nd AP can not be produced whatever the strength of the stimulus Length: from FL to early part of repolarization Causes: inactivation of Na+ channels Relative refractory period: Def.; the period during which membrane can produce another action potential, but requires stronger stimulus. Length: from after the ARP to the end of the AP Causes: some Na+ channels are still inactivated K + channels are wide open. FL Increased excitability ARP RRP

35 Factors affecting Membane potential & Excitability Factors excitability: * Role of Na+ 1) Na permeability (veratrine & low Ca 2+). Factors excitability: 1) Na permeability( local anaesthesia & high Ca2+) [ membrane stbilizers] Decrease Na+ in ECF: decreases size of AP, not affecting RMP Blockade of Na+ channels by tetradotoxin TTX decrease excitability & no AP ** Role of K+: 1) K extracellularly (hyperkalemia). 2) K extracellularly (hypokalemia): familial periodic paralysis 3) blockade of K+ channels by TEA: prolonged repolarization& absent hyperpolarization *** Role of Na+ K+ pump: only prolonged blockade can affect RMP & AP

36 Accommodation of nerve fiber Slow increase in the stimulus intensity gives no response: 1- inactivation of Na+ Channels 2- opening of K+ Channels

37 Conduction in an Unmyelinated Axon The action potential generated at one site, acts as a stimulus on the adjacent regions During reversal of polarity, the stimulated area acts as a current sink for the adjacent area A local circuit of current flow occurs between depolarized segment & resting segments (flow of +ve charges) in a complete loop of current flow The adjacent segments become depolarized, FL is reached, AP is generated Figure 7-18

38 Conduction in Myelinated Axon (Saltatory conduction) Myelin prevents movement of Na + and K + through the membrane. The conduction is the same in unmyelinated nerve fibers Except that AP is generated only at Nodes of Ranvier AP occurs only at the nodes. AP at 1 node depolarizes membrane to reach threshold at next node. The +ve charges jump from resting Node to the the neighbouring activated one (Saltatory conduction). Figure 7-19

39 Importance of saltatory conduction: velocity of nerve conduction. Conserve energy for the axon.

40 Orthodromic & antidromic conduction Orthodromic: from axon to its termination Antidromic: in the opposite direction Any antidromic impulse produced, it fails to pass the 1 st synapse & die out

41 Monophasic &biphasic AP Monophasic AP: recorded by one microelectrode inserted inside the fiber & one indifferent microelectrode on the surface. Biphasic: two recording electrodes on the outer connected to CRO

42 Depolarization & repolarization of a nerve fiber RMP does not record any change Depolarization flows to the +ve electrode... Upright deflection (+ve wave) Complete depolarization... No flow of current (baseline) Repolarization to the +ve electrode...down deflection Complete repolarization... No flow of current (baseline)

43 Action potential in a nerve trunk Nerve trunk is made of many nerve fibers The AP recorded is compound action potential, having many peaks The individual fibers vary in: 1- threshold of stimulation 2-distance from stimulating electrode 3- speed of conduction

44 Compound AP Graded Subthreshold; no response occurs Threshold; a small AP, feww nerve fibers Further increasing; AP amplitude increases up to a maximal Increasing the intensity, supramaximal stimuli, no more increase in the AP

45 Nerve fiber types According to their thickness, they are divided into: diameter conduction Spike duration Remarks A fibers 2-20 micron m/s 0.5 msec Alpha, beta, gamma & delta Most sensitive to pressure B fibers 1-5 micron 5-15m/s 1msec Preganglionic autonomic f Most sensitive to hypoxia C fibers <1 micron 0.5-2m/s 2msec Postganglionic autonomic f Most sensitive to local anesthetics

46 Metabolism of the nerve Rest: nerve needs energy to maintain polarization of the membrane, energy needed for Na+/K+ pump, derived from ATP. Resting heat Activity: pump activity increases to the 3 rd power of Na+ concentration inside, if Na+ concentration is doubled, the pump activity increases 8 folds;2 3. Heat production increases: 1- initial heat during AP 2- a recovery heat, follows activity =30 times the initial heat Neurotrophins: Proteins necessary for neuronal development, growth & survival Secreted by glial cells, muscles or other structures that neuron innervate Internalised & retrograde transported to the cell body

47

48 Neuromuscular Junction Def: it is the area lies between the nerve ending of the alpha motor neurons and skeletal muscle. Structure of the NMJ : 1) terminal knobs 2)Motor End Plate (MEP) 3)Synaptic cleft contain Ach vesicle contain Ach receptors contain choline estrase Steps Of Neuromuscular Transmission: 1) Arrival of action potential : permeability to Ca2+.. Rupture of vesicles. 2) Postsynaptic response: conductance to Na and K more Na influx end plate potential 3) EPP: graded, non propagated response that act as a stimulus that depolarizes the adjacent membrane to firing level AP. Muscle contraction. 4) Acetyl choline degradation end plate

49

50 Neuromuscular junction Properties of neuromuscular transmission: 1) unidirectional: from nerve to muscle 2) delay: 0.5msec 3) fatigue: exhaustion of Ach vesicles. 4) Effect of ions: Ca.. release of Ach Mg. release of Ach 5) Effect of drugs: * Drugs stimulate NMJ Ach like action Metacholine, carbachol, nicotine small dose. inactivating choline esterase neostigmine, physostigmine, diisopropyl phlorophosphate. * Drugs block NMJ: curare competes with Ach for its receptors

51 Motor end plate is a highly specialized region of the muscle plasma membrane.

52 Types of muscles Skeletal muscle: under voluntary control 40% of total body mass. Cardiac muscle: not under voluntary control. Smooth muscle: not under voluntary control. Both are 10% of total body mass

53 Skeletal muscles Attached to bones >400 voluntary skeletal muscles Contraction depends on their nerve supply 4 functions: 1- force for locomotion & breathing 2- force for maintaining posture & stabilizing joints 3- heat production 4- help venous return

54 Morphology Muscle fibers: Bundled together by C.T. Arranged in parallel between 2 tendenious ends Is a single cell Closely enveloped by glycoprotein sheath (sarcolemma) outside the cell membrane Made of many parallel myofibrils embeded in a sarcoplasm, between a complex tubular system

55 Skeletal muscle Each muscle fiber is a single unit. It is made up of many parallel myofibrils embedded together and a complex sarcotubular system. Each muscle fibril contains interdigitating thick and thin myofilaments arranged in sarcomeres. 2 major proteins: 1- thick filaments [myosin] 2- thin filaments [actin, troponin, troopomyosin] Troponin & trpomyosin regulate muscle contraction by controlling the interaction of actin & myosin

56 The sarcomere It is the functional unit of the muscle. It ext\ends between two sheets called Z lines. Thick filaments (Myosin) in the middle (dark band (A)). Thin filaments on both sides (light band (I) ). Z line in the middle of I band. H zone in the middle of A band. When the muscle is stretched or shortened, the thick & thin filaments slide past each other, and the I band increases or decreases in size

57 Internal organization:

58 Striations:

59 Myofilaments 1- thick filaments (myosin): 300 myosin molecules 2 heavy chains & 4 light chains Each myosin molecule has two heads attached to a double chains forming helix tail. myosin head contain actin binding site, an ATP- binding site and a catalytic site (ATPase). Each myosin head protrude out of the thick filaments forming cross bridges that can make contact with the actin molecule 2- Thin filaments (actin) Actin, tropomyosin, troponin. Actin is a double helix that has active sites for combines with myosin cross bridges. Troponin: 3 subunits I for Actin binding, T for tropomyosin binding, C for Ca binding.

60

61 Sarcotubular system Consists of T-tubules and Sarcoplasmic reticulum. T tubules consists of network of transverse tubules surround each myofibril, at the junction of the dark and light bands. T tubules are invaginations from cell membrane. T tubules contain extracellular fluid.r T tubules transmit the AP from the surface to the depth of the muscle fiber. Sarcoplasmic reticulum: surrounds each myofibril, run parallel to it Sarcoplasmic reticulum: extends between the T tubules. Sarcoplasmic reticulum: are the sites for Ca storage. Sarcoplasmic reticulum ends expands to form terminal cistern, which makes specialized contact with the T tubules on either side Foot processes span the 200 A 0 between the 2 tubules SR contains protein receptor called Ryanodine that contains the foot process and Ca channel T tubule contains voltage- senstive dihydropyridine receptor that opens the ryanodine channel

62

63 Electrical changes in the muscle Similar to nerve action potential: RMP: -90mv AP lasts 2-4msec &precedes muscle contraction by 2msec Single muscle fiber obeys all or none rule

64

65 Muscle Twitch a single action potential causes a brief contraction followed by relaxation The twitch starts 2msec after the start of depolarization, before the repolarization is complete

66 Excitability changes It is like changes that occurs in the nerve (refractory) during action potential The refractory period ends at the time of beginning of contraction, so during contraction, the excitability is normal, can respond to another stimuli AP Mechanical changes

67 Mechanical changes [excitation-contraction coupling] Action potential produce muscle contraction in 4 steps; 1- release of Ca2+: AP pass through T tubules, causing Ca release from the terminal cistern into the cytoplasm 2- activation of muscle proteins: Ca2+ binds troponin, moves tropomyosin away from active site of actin, actin binds with myosin, contraction starts 3- generation of tension: binding, bending, detachment, return 4- relaxation: active process, when Ca is removed frrom the cytoplasm & actively pumped into the SR

68 Action Potentials and Muscle Contraction

69 Mechanism of muscle contraction

70 Cross-bridge formation:

71 Types of Muscle Contractions Isotonic: Change in length (muscle shortens) but tension constant Isometric: No change in length but tension increases e.g. Postural muscles of body Muscle contraction in the body is a mixture of both types e.g. when person lifts a heavy object, the biceps starts isometric, then isotonic contraction

72 Factors affecting muscle contraction 1- type of muscle fiber: Slow red fiber: Slow contraction & relaxation, rich in myoglobin, not easily fatigued, adapted for prolonged weight bearing, e.g. soleus muscle Rapid pale fiber: rapid contraction & relaxation, poor myoglobin, easily fatigued, adapted for skilled movements, e.g. hands & extraocular muscles 2- type of load: Preload: load applied to the muscle before contraction changing its initial length, [within limits, the more the initial length, the more the tension in isometric contraction] Afterload: load added to the muscle after it starts contraction [the more the after load, the less will be the velocity of contraction 3- stimulus factor: Stimulus strength: the more strength of the stimulus, the more the fibers stimulated, the more force of contraction Stimulus frequency: low frequency; separate twitches Medium frequency; clonus High frequency; tetanus 4- fatigue: repeated stimulation of the muscle results in fatigue due to: Depletion of ATP,CP & glycogen consumption of acetyl choline Accumulation of metabolites decreased O2 & nutrient supply