Effects of [Ca²⁺] and [Mg²⁺] on the decay of miniature endplate currents

Abstract

THE endplate current at the neuromuscular junction is initiated by the combination of acetylcholine (ACh) with its receptor. The current rises rapidly to a maximum, and then decays exponentially¹. The rate of decay of the endplate current (e.p.c.) depends on membrane potential; hyperpolarisation lengthens the decay phase^2,3. A plausible hypothesis for this is that the rate of disassociation of the ACh from the receptor depends on the voltage gradient through the membrane⁴. The membrane potential consists of three components: the voltage gradient through the membrane itself and the surface potentials at the two membrane–solution interfaces. The surface potentials are thought to be negative, owing to an excess of negatively-charged groups on the membrane phospholipids. An elevation in the divalent ion concentration in the extracellular solutions reduces the negativity of the external surface potential, either by binding to the phospholipids or by screening the charges. A lowering of the negativity of the external surface potential leads to a corresponding increase in the voltage gradient within the membrane (over shorter periods than for phospholipid flip-flop to occur). This leads to the prediction that alterations in the extracellular [Ca²⁺] or [Mg²⁺] are likely to change the time course of the e.p.c. Our experiments were designed to test this hypothesis.