Pharmacology, structure and function of cardiac L-type Ca(2+) channels

Voltage-gated L-type Ca(2+) channels control depolarization-induced Ca(2+) entry in different electrically excitable cells, including mammalian heart. Important molecular and functional details providing new insight into L-type channel structure and modulation are reviewed in this article. This includes the identification of amino acid residues responsible for drug binding, the role of accessory subunits and alternative splicing for fine-tuning channel activity and modulation by protein kinases (A, C, tyrosine kinases), cGMP-dependent pathways, calmodulin and Ca(2+). Alterations in Ca(2+) channel activity under pathological conditions such as in heart failure or during ischemia could provide new clues for the development of drugs to treat cardiovascular diseases.