Modulation of Calcium Channels in Cardiac and Neuronal Cells by an Endogenous Peptide

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Abstract
Calcium channels mediate the generation of action potentials, pacemaking, excitation-contraction coupling, and secretion and signal integration in muscle, secretory, and neuronal cells. They physiological regulation of the L-type calcium channel is thought to be mediated primarily by guanine nucleotide-binding proteins (G proteins). A low molecular weight endogenous peptide has been isolated and purified from rat brain. This peptide regulates up and down the cardiac and neuronal calcium channels, respectively. In cardiac myocytes, the peptide-induced enhancement of the L-type calcium current had a slow onset (half-time .apprxeq. 75 seconds), occurred via a G protein-independent mechanism, and could not be inhibited by .alpha.1-adrenergic, .beta.-adrenergic, or angiotensin II blockers. In neuronal cells, on the other hand, the negative effect had a rapid onset (half-time < 500 milliseconds) and was observed on both T-type and L-type calcium channels.