Endplate potential

Stimulation of the motoneuron releases acetylcholine onto the muscle endplate and results in contraction of the muscle fiber. Contraction and associated electrical events can be produced by intra-arterial injection of ACh close to the muscle. Since skeletal muscle does not possess inherent myogenic tone, the tone of apparently resting muscle is maintained by spontaneous and intermittent release of ACh. The consequences of spontaneous release at the motor endplate of skeletal muscle are small depolarizations from the quantized release of ACh, termed miniature endplate potentials (MEPPs) [15] (seeCh. 10). Decay times for the MEPPs range between l and 2 ms, a duration similar to the mean channel open time seen with ACh stimulation of individual receptor molecules. Stimulation of the motoneuron results in the release of several hundred quanta of ACh. The summation of MEPPs gives rise to a postsynaptic excitatory potential (PSEP),... 

Wagley48 found that V produced a dose-related decrease in the endplate potential of the curarized iliofibularis muscle of the frog at 1-3 x 10 2 m. A similar effect of 2-PAM I was found at 1-3 x 10-3 M, whereas concentrations below 10 3 M produced dose-related increases in the endplate potential. Fleisher et al.47 found that III, unlike I, had no excitatory action on the Isolated frog rectus abdominis, but had a more potent effect than I in inhibiting the response of that muscle to decamethonlum, carbamylcholine, and acetylcholine. 

The transmitter is present throughout the cholinergic neurones and exists within the axon terminals in vesicles. About 1% of the vesicles are the readily releasable store that maintains transmitter release but more than 80% is in motor nerve endings in the releasable store, which is released in response to a nerve impulse. The remainder of ACh is in the so-called stationary store. The release of ACh may be spontaneous or in response to nerve impulses. Spontaneous release of ACh results in the production of random miniature endplate potentials. It is, however, in response to a nerve impulse that we see a large release of ACh provided there is adequate calcium present in the extracellular fluid. Evoked release of ACh usually results in the production of an endplate potential due to depolarisation of the motor endplate. 

Furthermore, it was observed that the oxime HI-6 might show direct pharmacological effects in the cholinergic nervous system in skeletal muscles. It has been found that HI-6 reduces the miniature endplate potentials and increases the quantal content by a dose-dependent decrease in the miniature endplate potential amplitude (Melchers et al., 1991). Other possible explanations have been suggested for oximes at other targets in the nervous system, such as... 

Normally, a single nerve Impulse in a terminal motor axon liberates enough ACh to produce a localized depolarization (the endplate potential) that initiates a propagated muscle action potential. The liberated ACh is rapidly hydrolyzed by AChE, and the muscle relaxes. Therefore, each motor-nerve Impulse initiates only one muscle contraction. After oartial inhibition of AChE. however. 

Eccles, J.C. and MacFarlane, tf.V., 1949 Actions of Anticholinesterases on endplate potential of frog muscle J. Heurophyslol. 12 59-80. 

Spontaneous release of acetylcholine, as measured electrophysiologically as increased miniature endplate potential (MEPP) frequency, was determined in myofibers from rat hemidiaphragms exposed to 2,4-DNP and/or methylmercury (Levesque and Atchison 1987). Tissues exposed to... 

The acetylcholine diffuses across the gap between the nerve terminal and the muscle membrane, (the neuromuscular cleft) and binds to receptors on the muscle surface. This results in the opening of Na /K channels and Na flows down its concentration gradient into the muscle. This ion flux causes a localised depolarisation, termed an "endplate potential", in the muscle. This nerve-evoked electrical disturbance can be measured using a microelectrode inserted into the muscle cell at the neuromuscular junction region and compared to a reference electrode. When the amplitude of this depolarisation reaches a threshold level a regenerative electrical depolarisation, known as an "action potential" is triggered in the muscle. This action potential is transmitted into the muscle cell where it triggers contraction of the muscle fibre. At the mammalian neuromuscular junction there is normally a 1 1 relationship between nerve action potentials and muscle action potentials. 

Acetylcholine vesicles fuse with the presynaptic membrane at a low rate to release their packets of transmitter even in the absence of nerve action potentials. This spontaneous release is random. It is insufficient to trigger an action potential in the muscle but can cause a small depolarisation of the membrane, termed a miniature endplate potential The smallest depolarisation is caused by release of the contents of a single vesicle, or one quantum of acetylcholine. After release the synaptic vesicle membrane is rapidly taken up into the nerve terminal and reutilised. The acetylcholine is broken down in the cleft to acetate and choline in a reaction catalysed by the enzyme acetylcholine esterase which resides in the neuromuscular cleft and the choline is taken back up into the nerve terminal where it participates in the synthesis of new transmitter. 

Botulinum toxin causes a large reduction in the amplitude of nerve-evoked endplate potentials. It does not reduce the amplitude of the smallest spontaneous miniature endplate potentials but it... 

Other potential antagonists of BoNT such as elevated calcium, calcium ionophores, lanthanum, black widow spider venom, 2,4-dinitrophenol, and agents that raise cyclic AMP levels were examined for their ability to reverse BoNT toxicity. Addition of the above compounds to BoNT-intoxicated preparations led to increases in the frequency of spontaneous miniature endplate potentials (MEPP) but resulted in little or no enhancement in the amplitude of evoked endplate potentials (EPP)." " Since these compounds generally increased spontaneous but not evoked activity, they were not considered to be of practical value for treatment of BoNT intoxication. 

The mechanism of the paralysis by the calabash curare alkaloids appears to be truly curariform. Van Maanen (81) showed that they act in the same manner as d-tubocurarine in antagonizing acetylcholine, and Paton and Perry (82) showed that muscles paralyzed by toxiferines respond to direct stimulations and give typical endplate potentials, all of which indicates true myoneural block. 

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