Evoked endplate potentials

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 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. 

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. 

To assess the effect of drugs on a neuromuscular synapse, either the endplate potentials or the intensity of muscular contractions in response to rhythmic electric stimulation of the nerve are registered In the first case, the evoked gradual responses of the neuromuscular junctions are recorded by means of thin electrodes. Changes in the magnitude of these responses are criteria of the efficiency of the drugs with respect to naptic transmission. In the second case, the facilitation or inhibition of synaptic transmission is reflected by either an increase or a decrease in the intensity of muscular contractions. For convenience, the latter are usually transformed into corresponding oscillations of electric current. 

Pumiliotoxin B had calcium-dependent effects on evoked release of acetylcholine from nerve terminals in frog neuromuscular preparations 26). The alkaloid in a dose and stimulus-dependent manner caused repetitive endplate potentials in response to a single stimulation of nerve. This effect on neurotransmitter release was strongly calcium-dependent and probably involved facilitation by pumiliotoxin B of evoked calcium transport through plasma membranes and/or membranes of the endoplasmic reticulum of the nerve terminal. 

Quantal analysis defines the mechanism of release as exocytosis. Stimulation of the motor neuron causes a large depolarization of the motor end plate. In 1952, Fatt and Katz [11] observed that spontaneous potentials of approximately 1 mV occur at the motor endplate. Each individual potential change has a time course similar to the much larger evoked response of the muscle membrane that results from electrical stimulation of the motor nerve. These small spontaneous potentials were therefore called... 

---