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Structure-functional diversity of human L-type Ca2+ channel: perspectives for new pharmacological targets.

Abstract
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.
AuthorsDarrell R Abernethy, Nikolai M Soldatov
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 300 Issue 3 Pg. 724-8 (Mar 2002) ISSN: 0022-3565 [Print] United States
PMID11861774 (Publication Type: Journal Article, Review)
Chemical References
  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Dihydropyridines
Topics
  • Amino Acid Sequence
  • Animals
  • Calcium Channel Blockers (pharmacology)
  • Calcium Channels, L-Type (chemistry, drug effects, genetics, metabolism)
  • Dihydropyridines (chemistry, pharmacology)
  • Genome
  • Humans
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Structure-Activity Relationship

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