Calcium Cooperativity in Calcium Entry and Calcium Action, and its Implications with Regard to Facilitation, at the Mouse Motor Nerve Terminal

Abstract

It is now well established that the coupling of neurotransmitter release to depolarization of nerve terminals depends upon influx of Ca²⁺ from the external medium via voltage-regulated cation-selective channels (reviews, 1, 2, 3). At the vertebrate neuromuscular junction this dependence is manifest in essentially the same way for release provoked by nerve impulses (i.e., end-plate potentials, EPPs) or release manifest as a raised frequency of miniature end-plate potentials (fmepp) induced by intermittent and graded depolarization of nerve terminals by extrinsically-applied currents or by steady depolarization of nerve terminals using raised K⁺ (4, 5, 6). The observation that EPP height can be proportional to the fourth power of the external Ca²⁺ (7, 8) has led to the proposition that four atoms of Ca²⁺ are required for the release of each package or “quantum” of neurotransmitter (8). In the first part of this paper there will be presented three independent lines of evidence indicating that this high apparent cooperativity is compounded of two elements: (a) a cooperativity of 2 for entry of Ca²⁺ into the nerve terminal and (b) a cooperativity of about 2 (at most 3) for transmitter release by internal Ca²⁺ .