Equivalence of Ca²⁺ and Sr²⁺ in transmitter release from K⁺-depolarised nerve terminals

Abstract

Depolarisation–secretion coupling at presynaptic nerve terminals is thought to be mediated by the influx of calcium ions from the extracellular fluid through voltage-sensitive channels in the nerve terminal membrane¹. In physiological conditions, the depolarisation is accomplished when the nerve action potential invades the nerve-ending. At the neuromuscular junction, the nerve impulse promotes the synchronous release of many quanta of the transmitter, acetylcholine, the response to which is recorded postsynaptically as the endplate potential (e.p.p.)². Strontium can substitute for Ca²⁺ in the support of transmitter release evoked by nerve impulses^3–5, although it is far less effective (on a molar basis) in the generation of the e.p.p. It has been suggested⁵ that Sr³⁺ may be less accessible from the extracellular fluid during the action potential, and might not achieve as high a concentration as Ca²⁺ in the nerve ending so that it would seem less effective. Alternatively, intra-terminal releasing sites may exhibit true selectivity for divalent cations. To help distinguish between these possibilities, I have made use of the long-established observation that when nerve terminals are depolarised by elevating the extracellular potassium ion concentration ([K⁺]₀), there is a dramatic increase in the frequency of spontaneous miniature endplate potentials (m.e.p.ps)^6–9. This is thought also to be a form of depolarisation-secretion coupling (that is, mediated by Ca²⁺ entry through voltage-gated channels), though of relatively long duration. I have compared the relative abilities of Ca²⁺ and Sr²⁺ in supporting the augmented m.e.p.p. frequency seen in high K⁺ Ringer's solutions and report here that they are qualitatively and quantitatively equivalent, in contrast to their differences in the nerve impulse-evoked e.p.p.