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Vol. 300, Issue 3, 724-728, March 2002

Structure-Functional Diversity of Human L-Type Ca2+ Channel: Perspectives for New Pharmacological Targets

Darrell R. Abernethy and Nikolai M. Soldatov

Section on Molecular and Clinical Pharmacology, Laboratory of Clinical Investigation, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland

The L-type Ca2+ channels mediate depolarization-induced influx of Ca2+ into a wide variety of cells and thus play a central role in triggering cardiac and smooth muscle contraction. Because of this role, clinically important classes of 1,4-dihydropyridine, phenylalkylamine, and benzothiazepine Ca2+ channel blockers were developed as powerful medicines to treat hypertension and angina pectoris. Molecular cloning studies revealed that the channel is subject to extensive structure-functional variability due to alternative splicing. In this review, we will focus on a potentially important role of genetically driven variability of Ca2+ channels in expression regulation and mutations, Ca2+-induced inactivation, and modulation of sensitivity to Ca2+ channel blockers with the perspective for new pharmacological targets.

0022-3565/02/3003-0724$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2002 by U.S. Government


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