Neuro-Muscular Junction:• Ach released in quanta.• Each quanta – 10000Ach• Three stores of Achquanta.– Primary(1000 quanta)– Secondary(10000)– Reserve(100000)
• Calcium influx at depolarized presynapticjunction.• Calcium influx α Ach released.• Ach binds to AchR on post synaptic membranefold crests.• Sodium channels open to produce End PlatePotentials (EPP)• EPP α Amount of Ach binding to AchR.• EPP above threshold produces an all or noneMuscle Fiber Action Potential (MFAP)
• Safety Factor: The amplitude of EPP abovethreshold value required to generate a MFAP.• Ach broken up in the synaptic cleft by Achesterase.• Choline taken up in to presynaptic cleft.
Physiologic modeling of RNS:1. M= pn– M: number of quanta released– P : probability of release (0.2)– N: number of quanta in primary store(1000)2. Secondary store replenishes the primary after 1to 2 seconds.3. 100msec required to pump calcium out ofpresynaptic terminal– Stimulation rated > 10hz cause calcium accumulation.
Modeling of Rapid RNS(30-50Hz):With rapid RNS, the Depletion of quanta iscounterbalanced by(1) increased Mobilization of quanta from thesecondary to the primary Store(2) (2) calcium accumulation in the presynapticterminal increases p, the probability of release.
Exercise testing:• Subject asked to voluntarily contract musclewith maximum force.• Motor units fire at maximal rate (30-50Hz).• Same effects as Rapid RNS.• Effects occur with brief periods of excercise(typically 10 sec).– Post exercise or post tetanic facilitation.
LAB Practice:• Postexercise facilitationand exhaustion Three-Hertzrepetitive nervestimulation in a patient withmyasthenia gravis• A: Decrement of compoundmuscle action potential(CMAP) amplitude at rest.• B: Postexercise facilitation,Decrement of CMAPimmediately following 10seconds of maximalvoluntary exercise hasrepaired toward normal.
Important points:• Immobilization and isometric electrodeposition.• Supramaximal stimulus• Temperature must be controlled• AchI withheld 4 hrs prior to study.• Proximal site better than distal site– Distal easy; proximal difficult.