Nerve And MR PDF

NERVE MR 0 Neuron Structural unit of the nervous system Specialized cell for rapid transfer & integration of information Formed of 1. Soma= cell body= processing center 2. Dendrites (↑ surface area): receive signals 3. Axon (n...

NERVE MR 0 Neuron Structural unit of the nervous system Specialized cell for rapid transfer & integration of information Formed of 1. Soma= cell body= processing center 2. Dendrites (↑ surface area): receive signals 3. Axon (nerve fiber) o Originates from (axon hillock) o End in many Synaptic Knob: Contain transmitter vesicles or granules o Axon may be short (few mm) if terminate on nearby cell (as in CNS) or long (many cm) if terminates on distant cells (skeletal muscle) Synapse: area of contact between presynaptic and postsynaptic neuron Types of nerve fibers A- According to myelination Myelinated Nerve (thick) Un-Myelinated Nerve (thin) Axon is surrounded by myelin sheath, made by Axon is surrounded by Schwann Schwann cells without formation of myelin Myelin: insulator→ ↓ion flow through membrane Interrupted by Nodes of Ranvier: non-insulated area → ions can move across the membrane with little resistance A & B fiber C B- According to thickness & velocity & sensitivity to environmental factors A (α, β, γ, δ) B C Diameter 2-20 micron 1-5 micron (µ) < 1 micron Velocity= rate of conduction 20-120 m/sec 5-15 m/sec 0.5- 2 m/sec Duration spike 0.5 msec 1 msec 2 msec Example Somatic motor Preganglionic autonomic Postganglionic autonomic Blocked by Pressure Hypoxia Anesthesia Affect C fibers before A B fibers are most susceptible to hypoxia, C fibers least affected 1  Resting membrane potential (RMP)=polarized state Definition Potential difference between inside (negative) and outside of the membrane at rest -90 mv in large nerve & large skeletal muscle fibers -70 in medium sized neurons -20→ -40 in less-excitable cells (RBCs, epithelial cells) Recording 2 microelectrodes (one inside and other outside fiber) connected to voltmeter. (cathode ray oscilloscope) Causes of RMP u==unequal distribution of ions, caused by A- Selective permeability of membrane (diffusion): main factor 1. Intracellular K+ concentration > outside (140/4) = (35/1) 2. Intracellular Na+ concentration < outside (14/140) = (1/10) 3. Each ion tries to reach equilibrium potential 4. Resting membrane is permeable to K+ (100 times) via leakage- (non-gated) K+ channels > Na+ (K+ outflow > Na+ inflow) 5. Resting membrane is impermeable to intracellular anions (protein) 6. Net effect →inside become negative to outside = potential difference is generated 7. Causes = -86mv (93 %) Leak K = see later ? B- Na+-K+ Pump 1. Electrogenic pump Pump 3 Na+ ions out & 2 K+ ions in against concentration gradient (3:2) 2. Result: more +ve ions outside 3. Causes = -4 mv (7%) 2 Role (contribution) of Ion fluxes & Na+-K+ Pump to R.M.P. 1. Contribution of the selective permeability for K+, Na+ A-Nernst equation: calculate equilibrium potential for any univalent ion at normal body temperature concentration inside E (millivolt) = ± 61 x log concentration outside the sign is positive when the ion is negative (vice versa) I- If K+ is the only ion diffuse via the cell membrane (only factor causing RMP) RMP = equilibrium potential for K+ [𝐾+ ]𝑖𝑛 𝐸𝐾 + = - 61 mV. X log [𝐾+ ]𝑜𝑢𝑡 EK + = -61 mV. X log 35 = -94 mv II- If Na+ is the only ion diffuse via the cell membrane RMP = equilibrium potential for Na+ 1 𝑬𝑵𝑎+ = - 61 mV. x Log = + 61 mv 10 B. Goldman Equation: calculates RMP more accurate by involving Concentration of Na+, K+ , Cl- inside and outside. Relative Permeability of the membrane to each ions [𝐶𝑁𝑎+𝑖 X PNa ] + [𝐶𝐾 + i X P𝑘 ] + [𝐶Cl − o X PCl − ] 𝐸(𝑚𝑖𝑙𝑙𝑖𝑣𝑜𝑙𝑡𝑠) = −61𝑋𝐿𝑜𝑔 + + [𝐶𝑁𝑎 + o X PNa ] + [𝐶𝐾 𝑜 𝑋 P𝑘 ] + [ CCl − i X PCl − ] R.M.P. caused by diffusion of ion = - 86 mV. [95 % of R.M.P.] near to K equilibrium potential therefore change in K conc. →leads to marked & serious effects on nerves & muscles) 2. Contribution of Na+-K+ Pump to R.M.P Electrogenic pump Causes = -4 mv of RMP At equilibrium potential: Flow of ion in one direction is balanced by its flow in opposite direction Equal rate of ion influxes and effluxes 3  Action Potential Definition rapid change in potential following stimulation by threshold (adequate) stimulus Recording as before Shape, phases of Action Potential (diagram): A. Latent period (Isoelectric interval between application of stimulus & start of action potential) Time taken impulse to travel from stimulating to recording electrode. Duration depends on distance between 2 electrodes & speed of conduction in nerve fiber Velocity of conduction= distance between stimulating & recording electrodes/ latent period B. Action potential consists of 3 phases 1. Depolarization: (Ascending Limb) Slow phase (-90 to -65 mv) (firing level) (first 25 mv depolarization) Rapid phase (-65 to zero (iso-potential) then overshoot to +35mv (reversal of polarity) Amplitude of action potential = 90+35= 125 mv 2. Repolarization: (Descending limb) Rapid phase: first 70% Slow phase: 30% at the end , RMP is reached 3. Hyperpolarization Potential overshoot in opposite direction →form slight, prolonged hyperpolarization Then RMP is reached gradually Duration of action potential: spike (shar rise & fall) = 2ms, hyperpolarization=35-40 ms 4  Ionic basis of action potential Depolarization caused by Na+ inflow, Repolarization caused by K+ outflow through Voltage gated Na+ channel: 2 gates; outer activation and inner inactivation gate. At RMP, the activation gate is closed, while the inactivation gate is open Voltage gated K+ channel: with only one inner activation gate. Once nerve is stimulated, the gates move in sequence a- outer Na+ gates open→ activate Na+ channel b- inner Na+ gates close→ inactivate Na+ channel c- K gates open→ activate K+ channel 1. Depolarization (positive feedback) (regenerative process) (Na+ inflow) A. Slow phase (-90 to -65 mv) Stimulus → cause initial depolarization (decrease in membrane potential from -90 mv to firing level Some of activation gates of Na + channels open → Na+ inflow → cause further depolarization → more activation gates open →Until reaching -65mv (firing level or threshold) B. Rapid phase (-65 to +35mv) Opening of all Na channels → rush of Na+ in → (Ascending Limb) (Action potential will not occur until depolarization reaches firing level) then, rapid inactivation of Na+ channels starts. (Gates remain inactive for few msec. before returning to resting state) 3. Repolarization: (Descending limb Cause: Inactivation of Na+ channels→ limit Na influx & terminate depolarization Activation of K+ channels open shortly after opening of Na channel (opening is slower and more prolonged than Na+ channels)→ K outflow 4. Hyperpolarization Cause: slow closure of K+ channels.→ → higher K conductance than at rest. Leakage K+ Channel: non gated, voltage sensitive channels, drive K+ ions inward only in hyperpolarization, drive the membrane potential to the resting state Re-establishment Na & K gradient after action potential by Na+-K+ pump ?? A.P. obeys All or None Rule: (once produced→ propagate with the same amplitude, Duration, shape) regardless stimulus strength at or above threshold (suprathreshold) provided that all experimental conditions are kept constant 5  Excitability Changes during the Action Potential From initial depolarization to firing level: excitability ↑ Remaining of A.P.: 2 refractory periods→ ensures one-way forward propagation of AP. = protect the nerve from rapid repetitive stimulation Absolute refractory period (A.R.P.) Relative refractory period (R.R.P) excitability = zero excitability below normal Nerve cannot be stimulated Nerve cannot be stimulated unless stimulus > threshold whatever stimulus strength 2nd action potential cannot be elicited From firing level to early repolarization From end of Absolute refractory period till end of action potential (rest) Na channels are rapidly inactivated Some Na channels returned to resting state (active) (Inner gate is closed) K channels are opened during repolarization & hyperpolarization (more difficult to stimulate the nerve) 6  Local Response [Local Excitatory State] Definition local partial depolarization due to subthreshold stimuli Mechanism Subthreshold stimulus →open few Na channels→ slight depolarization (not enough to reach firing level and elicit action potential) followed by rapid repolarization to resting level Local response differs from A.P. in A. None propagated (magnitude is insufficient to generate another local response nearby, and it fades away within 1-2 msec.) B. Not obey all or none rule C. No refractory period D. Graded (magnitude, duration vary with size, strength of stimulus) E. Summated by rapid repeated subthreshold stimuli to reach firing level &generate action potential. F. During local response, nerve excitability is ↑, as potential moves towards firing level. Types of membrane potential Under resting conditions: RMP On stimulation: By threshold (adequate) stimuli: action potential By subthreshold (inadequate) stimuli: local response Accommodation of Nerve Fiber Definition Gradual “slow” increase in intensity of subthreshold stimulus to threshold level → produce no response Causes slow activation (opening) of Na+ channels →slow entry of Na+ , balanced by a) Inactivation (closure) of Na+ channels. b) Opening of K+ channels. 7  Excitability ability of living cells to respond to stimulus (change in environment). Membrane potential is the basis of excitability Stimuli: change or event which excite an organism → result in response Most excitable tissues: nerve and muscle Types of stimuli (electrical, mechanical, chemical, thermal) Electrical stimulus is preferred because ✓ Similar to natural stimuli inside the body chronaxie ✓ Controlled ✓ Measured ✓ Not cause tissue damage Strength duration curve Definition inverse relation between strength of stimuli & duration needed to produce an active response Factors affecting effectiveness of stimulus 1. Strength (intensity): 2. Duration Threshold stimuli (Rheobase): Minimal Utilization time: Time needed by rheobase to intensity needed to excite the nerve → A.P. excite the nerve (response) Sub-threshold stimuli→ produce Chronaxie: Time needed by stimulus double local response. rheobase to excite nerve. (index of nerve excitability) If excitability is high, chronaxie is shortened. ✓ Within limits: stronger the stimulus→ shorter the duration needed to excite the nerve ✓ Stimuli of extremely short duration whatever its strength→ produce no response 3. Rate of rise of stimulus intensity: Rapidly increased stimulus intensity to threshold → response. Slowly increased → produce no response [nerve accommodation]. 8  Conduction (propagation) of action potential A- Conduction in Unmyelinated nerve (continuous conduction) (passively) A.P. generated at on location acts as a stimulus for generation of new A.P. on adjacent area 1. During reversal of polarity→ potential difference between stimulated depolarized & adjacent resting polarized areas 2. +ve charge flow passively to –ve area on both outer & inner surfaces →local circuit of current flow. 3. Adjacent area becomes depolarized to firing level →produce action potential, while active area →return to resting level B- Conduction in Myelinated nerve (saltatory conduction) (not continuous) Same as unmyelinated, however, the cell membrane is exposed to ECF only at node of ranvier with numerous voltage gated Na channels 1. A.P. generated only at node, acts as a stimulus for generation of new A.P. on adjacent node 2. +ve charge jump from resting node to stimulated one (saltatory conduction). 3. ↑ diameter of the nerve fiber →↑intermodal distance →↑ speed of propagation (directly proportional) Importance of saltatory: ✓ ↑velocity of conduction (50 fold). ✓ Conserves energy Because only nodes depolarize →little energy (ATP) for reestablishing Na+ and K+ gradient by Na+ K+ pump Action potential generated, travel in both directions. Action potential magnitude does not change The original Action potential does not propagate along the nerve fibers but result in sequential generation of identical action potential Velocity of conduction ↑by: 1) square root of the fiber diameter 2) Myelination Arrival of action potential to synaptic knob cause release of chemical transmitter 9  Orthodromic and antidromic conduction Action potential generated (when initiated in the middle), travel in both directions. In living animal, travels in one direction, i.e. from synaptic junction or receptor along axon to termination (orthodromic conduction). Conduction in the opposite direction is called antidromic conduction Synapse (unlike axon), permits conduction in one direction only Any antidromic impulse fail to pass the first synapse and die out at this point Factors affecting Nerve Excitability 1. Role of Na+: ↑ Na+ permeability→ ↓ Na+ permeability (slowly depolarized) ↑ excitability ↓ excitability (membrane stabilizers) Veratridine Local anesthetics: cocaine ↓ Extracellular Ca concentration +2 ↑extracellular Ca+2 concentration (hypocalcemia) (hypercalcemia) + Blockade of Na channels by tetrodotoxin [TTX] →↓nerve excitability, and no A.P. ECF Na+ conc. [hyponatremia]→ ↓size of A.P. but has little effect on R.M.P. 2. Role of K+ ↑ ECF K+ concentration ↓ ECF K+ (hypokalemia) → Make RMP to (hyperkalemia) hyperpolarize→↓excitability Make RMP to depolarization Familial periodic paralysis: hereditary hypokalemia →↑excitability. → ↓excitability →no nerve impulses → Paralysis. (treated by intravenous K+ ) 3. Role of Na+ – K+ pump: Only prolonged blockade of Na+ K+ pump →affect R.M.P. and genesis of A.P 4. local response: Excitability is increased Membrane potential moves closer to firing Level (Threshold) Subthreshold stimulus →can produce A.P. 10 Monophasic and Biphasic Action Potential Monophasic action potential inserting one electrode inside & the other indifferent electrode outside Biphasic Action Potential 2 recording electrodes outside → following changes are observed a. At rest: no potential difference between 2 electrodes b. When impulse (wave of depolarization) reach 1st electrode (near to the stimulator)→ 1st electrode is negative relative to 2nd c. When impulse reach area between 2 electrodes→ zero potential difference d. When impulse reach 2nd electrode→ 1st electrode is positive relative to 2nd → wave is recorded in opposite direction. e. When impulse leaves 2nd electrode→ no potential difference N.B. Can be monophasic by crushing or destroying the nerve between 2 electrodes or region under 2nd electrode. 11 Action Potential in Nerve Trunk "Compound Action Potential" Definition Action potential recorded from nerve trunks or peripheral nerves (many nerve fibers). Characters 1. Has Many peaks: as each fiber in the nerve vary in: a. Threshold b. Distance from stimulating electrodes. c. Speed of conduction according to thickness. activity in fast-conducting fibers arrives at recording electrodes sooner than activity of slower fibers. 2. graded A- Subthreshold stimuli→ none of fibers are stimulated →no response. B- ↑ intensity to threshold → produce small action potential due to response of nerve fibers of low threshold. C- Further ↑in intensity → action potential ↑ in amplitude, up to maximum. (maximal stimulation). D- Supramaximal stimuli→ no further increase in the amplitude Neurtrophins: Certain proteins, secreted by glial cells, muscles, or other structures that the neurons innervate They are internalized and then transported by retrograde transport to neuronal cell body Necessary for neuronal development, growth, survival 12