Structure-functional diversity of human L-type Ca2+ channel: perspectives for new pharmacological targets.
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.
Abernethy
Darrell R
DR
Section on Molecular and Clinical Pharmacology, Laboratory of Clinical Investigation, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
Soldatov
Nikolai M
NM
D000595:Amino Acid Sequence; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004095:Dihydropyridines / Q000737:chemistry / Q000494:pharmacology; D016678:Genome; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines