Action of Calcium on the Secretory Process

Abstract

The chronology of events dictates that a discussion of the role of calcium in secretory mechanisms should begin with the cholinergic nervous system, for there is no doubt that this was the system where definitive studies implicating calcium as a regulator of neurotransmitter release were first conducted. In actuality, evidence for the involvement of calcium in acetylcholine release was presented many years before acetylcholine was identified as the chemical transmitter at cholinergic junctions. It was in 1894 that Locke immersed the frog sartorius muscle, with its attached nerve, in a saline solution lacking calcium. After 15–20 min the muscle failed to respond when its nerve was stimulated, although it did contract to direct stimulation. The addition of a small amount of calcium to the bath restored the response to nerve stimulation. The significance of this classical experiment, which established the importance of calcium in transmission of excitation from nerve to muscle, had to await the discovery by Loewi (1921, 1945) that the vagus nerve liberates a chemical substance which he termed “Vagus-stoff” before acetylcholine was identified as the chemical transmitter at the neuromuscular junction and autonomic ganglia. It was with these two cholinergic systems—as a consequence of the studies of Harvey and Maclntosh and of Bernard Katz and his associates—that the role of calcium in the release of acetylcholine was first clearly established.