The Electrostatic Basis of Mg ⁺⁺ Inhibition of Transmitter Release

Abstract

The inhibition by Mg ++ of stimulus-evoked transmitter release is attributed to a decrease in surface potential, Ψ 0 , on the outer surface of the presynaptic terminal and hence a lower surface calcium concentration, [Ca ++ ] 0 . Data on the frog neuromuscular junction are quantitatively fit by assuming that there is a negative charge density, σ, on the outer surface of the presynaptic terminal of 6.5 × 10 13 charges per cm 2 and that simple diffuse double layer theory is applicable. No specific binding of Mg ++ or Ca ++ is required. Without any additional assumptions, the inhibitory effect of univalent cations is also quantitatively predicted.

Sodium and calcium fluxes in a clonal nerve cell line.

“…We have already demonstrated the existence of such an exchange mechanism. (2) In Na+-free sucrose medium the effective concentration of Ca2+ at the cell surface may be increased due to lack of electrostatic screening by Na+ (Muller & Finkelstein, 1974). This increased availability of Ca2+ could enhance the fluxes we measure.…”

Surface charges and the effects of calcium on the frequency of miniature end‐plate potentials at the frog neuromuscular junction.

“…This suggests that the surface potential in usual frog Ringer solution is about -100 mV. Muller & Finkelstein (1974), studying possible surface charge effects on evoked release, fit their data with o-= 1 charge/154 A2, which would give a surface potential of -75 mV.…”

AN ESTIMATE OF THE EQUILIBRIUM DISSOCIATION CONSTANT FOR CALCIUM AS AN ANTAGONIST OF EVOKED ACETYLCHOLINE RELEASE: IMPLICATIONS FOR EXCITATION‐SECRETION COUPLING

“…Because of these complexities, it has been suggested that an ion such as Mg2+, rather than selectively binding to a negatively charged site in the fashion of a drug-receptor interaction, may inhibit release by nonselectively screening fixed negative charges associated with the external surface of the nerve terminal, thereby reducing the surface potential and the surface ICa2+1 near the Ca2+ conductance pathway (Muller & Finkelstein, 1974). This interpretation implies that Ca2 , in asserting its role as the physiological mediator of excitation-secretion coupling, need not bind to an external site on the motor nerve ending.…”

“…It would thus be of interest to have a method for determining the Kd for Ca2+ as an antagonist of evoked ACh release. If this value were considerably lower than the Kd for Mg2+, and represented antagonism at the same site as Mg2+, then the screening model (which predicts that ions of equal valency are equipotent in their effects) would be rendered untenable (Muller & Finkelstein, 1974).…”