Peripheral Nerve II Amelyn Ramos Rafael, MD Anatomical considerations 1
Physiologic properties of the nerve Irritability of the nerve A stimulus applied on the nerve causes the production of a nerve impulse, the nature of which is electrical RMP = -70mv polarized Transport properties of a resting nerve membrane 1. Active transport of Na+ and K+ ions through the membrane the Na-K pump Electrogenic pump (3 Na+ ions out for each 2K+ in) 2
2. leakage of K+ and Na+ through the nerve membrane The emphasis is more on K+ leakage What contributes to the establishment of the RMP? K+ diffusion potential Na+ diffusion through the nerve membrane Na+K+ + pump K+ diffusion potential Use the Nernst potential EMF (mv( mv) ) = +/- 61 x log (Ci( Ci/Co) An electrical potential across the membrane can exactly oppose the movement of ions through a membrane, despite concentration difference between the outside and inside if the potential is of proper polarity and magnitude. The potential that exactly opposes the movement of ions is the Np of that ion 3
Nerve Action Potential Voltage variations recorded Rapid changes in membrane potential Begins with a sudden change from the normal RMP (-)( ) to a (+) MP Ends with an almost equally rapid change back to the negative potential 4
Stages of AP Resting stage The membrane potential before the AP occurs Polarized Depolarization stage The membrane becomes permeable to sodium ions Polarized state lost overshoot Repolarization stage The sodium channels begin to close Potassium channels open Rapid diffusion of K+ to the exterior reestablishes the normal negative RMP 5
Overshoot: reversal of polarity Spike: the rapid decrease in potential After potential or after-depolarization: the slow return to resting levels Positive afterpotential or after hyperpolarization: : membrane potential goes lower than resting 6
Voltage-gated gated Sodium Channels Responsible for both depolarization and repolarization 2 gates: activation and inactivation Stages: 1. Resting: activation gate is close 2. Activated state: sodium ions pour inward Increased sodium permeability 500-5000 5000 fold 3. Inactivated state The same increase in voltage that opens activation gate also closes inactivation gate The membrane potential begins to recover back toward the resting membrane state (repolarization) Important characteristic 7
Voltage-gated gated Potassium Channels Resting state: gate is close, no K+ efflux Toward the end of action potential The voltage change causes a slow conformational opening of the gate Increased K+ diffusion through the channel 8
Voltage-gated gated Ca++ channels Slightly permeable to Na+ as well as to Ca++ Also called Calcium-Sodium channels or slow channels Numerous in cardiac and smooth muscles Sequence of events resulting from the application of an electrical stimulus on the nerve Increased membrane permeability to Na+ resulting in a sodium influx into the cell Rapid reduction of transmembrane voltage (depolarization) Further increase in membrane permeability to Na+ 9
Greater degree of depolarization (up to reversal of polarity) Decrease in membrane permeability to Na+ (inactivation) Gradual increase in membrane permeability to K+ increasing K+ efflux Restoration of RMP (repolarization( repolarization) Initiation of the AP A positive feedback vicious cycle opens the Na+ channels No AP as long as the membrane remains undisturbed The rising voltage cause many voltage- gated Na+ channels to begin opening Feedback continues until all channels are activated 10
Characteristics of AP Threshold stimulus and threshold voltage Stimuli of weak intensity may not cause the production of an AP A sudden rise in MP of 15-30mv is usually required (-90mv( to -65mv) All-or or-none response The magnitude of an AP is independent of the intensity of the stimulus The events of the AP are precise and reproducible 11
Strength-Duration relationship of stimulus The intensity of the stimulus required to initiate an AP is influenced by the duration of its application A weaker stimulus has to be applied for a longer period Refractory period Absolute Relative The second stimulus is ineffective because: Of sodium inactivation Later, slight sodium activation permit depolarization K+ conduction is still high; a greater depolarization is needed to make Na+ inflow greater than outflow 12
Properties of Mixed Nerves Maximal Stimulus the stimulus that produces excitation of all the axons Compound AP 13
Effects of subthreshold currents Local response or local excitatory state Not propagated Not all-or or-none, magnitude varies Undergoes summation (integration of inputs) Change in excitability If a subthreshold current is allowed to flow the region of the anode become less excitable (anelectrotonus( anelectrotonus) ) while the region of the cathode becomes more irritable (catelectrotonus) 14
Accomodation Failure to fire despite rising voltage Reason: if MP rises slowly the slow inactivating gates of the Na+ channels will have time to close at the same time that the activating gates are opening Requires a higher threshold voltage than normal to cause firing Slowly rising currents fail to fire the nerve because the nerve adapts to the applied stimulus Conductivity of the nerve Propagation of the AP An AP elicited at any one point in an excitable membrane usually excites adjacent portions of the membrane Sequential events: A potential difference arises between this region and the adjacent region 15
Local current flow from active to inactive region through the intracellular fluid and from this back to the active region through the interstitial fluid Membrane charge and voltage reduced in inactive region When threshold voltage is reached, an AP is generated The same process is repeated one after another in adjacent regions, in both directions Repolarization wave follows depolarization in both directions (constant speed and amplitude) 16
Saltatory conduction Occurs in myelinated or medullated nerve fibers Resting and AP generated only at the nodes of Ranvier Local circuit flow occurs between nodes Conduction speed is much faster 17
Faster conduction The membrane is more permeable to sodium If the RMP is lowered Amount of the charge stored per unit area is lesser Temperature is higher Fiber diameter is wider A fibers Types of nerve fibers Largest diameter axons (5-20um) Myelinated,, with brief ARP Conduction speed= 12-130 130 m/sec Examples: axons of sensory neurons that conduct impulses associated with touch, pressure, position of joints, and some thermal sensations 18
B fibers Axon diameter 2-32 3 um Longer ARP than A fibers Myelinated,, exhibit saltatory conduction at speeds up to 15 msec; ; conduct sensory nerve impulses from the viscera to the brain and SC Example: axons of the autonomic motor neurons C fibers Smallest diameter (0.5-1.5 um) Longest ARP Nerve impulse conduction = 0.5 2 m/sec Example: autonomic motor fibers that extend from the autonomic ganglia to stimulate the heart, smooth muscle, and glands 19
Numerical classification of sensory neurons Ia muscle spindle, annulo-spiral ending Ib from Golgi tendon organ II from flower-spray ending of muscle spindle and from some touch receptors III from pain and temperature receptors IV from pain, temperature, and other receptors 20