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lüll Structure-functional diversity of human L-type Ca2+ channel: perspectives for new pharmacological targets Abernethy DR; Soldatov NMJ Pharmacol Exp Ther 2002[Mar]; 300 (3): 724-8The 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.|Amino Acid Sequence[MESH]|Animals[MESH]|Calcium Channel Blockers/*pharmacology[MESH]|Calcium Channels, L-Type/*chemistry/drug effects/genetics/*metabolism[MESH]|Dihydropyridines/chemistry/pharmacology[MESH]|Genome[MESH]|Humans[MESH]|Molecular Sequence Data[MESH]|Promoter Regions, Genetic[MESH]|Structure-Activity Relationship[MESH] |