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

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 300; no. 3; pp. 724 - 728
• Main Authors: Abernethy, Darrell R., Soldatov, Nikolai M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2002; American Society for Pharmacology and Experimental Therapeutics
• Subjects: Amino Acid Sequence; Animals; Calcium Channel Blockers - pharmacology; Calcium Channels, L-Type - chemistry; Calcium Channels, L-Type - drug effects; Calcium Channels, L-Type - genetics; Calcium Channels, L-Type - metabolism; Dihydropyridines - chemistry; Dihydropyridines - pharmacology; Genome; Humans; Molecular Sequence Data; Promoter Regions, Genetic; Structure-Activity Relationship; FISH; DHP; nt; CaM; kb
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.300.3.724

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.