Large-conductance Ca2+-activated K+ channels: Physiological role and pharmacology

Sheng Nan Wu

Research output: Contribution to journalReview articlepeer-review

104 Citations (Scopus)


Large-conductance Ca2+-activated K+ (BKCa) channels differ from most of other K+ channels in that their activation is under dual control, i.e., activated by either increase in intracellular Ca2+ or membrane depolarization. These channels, which are widely distributed in a variety of cells, can control Ca2+ influx as well as a number of Ca2+-dependent physiological processes. In neurons or neuroendocrine cells, BKCa channels are believed to play an important role in controlling hormonal secretion by altering the duration and frequency of action potentials. The activity of BKCa channels functionally expressed in vascular endothelial cells can control K+ efflux and affect intracellular Ca2+ concentration. Experimental observations have revealed that a variety of compounds can directly modulate BKCa channel activity. Epoxyeicosatrienoic acids, a metabolite of arachidonic acid, and the increase in intracellular cyclic GMP with vinpocetine or YC-1 can stimulate BKCa channel activity. The increased activity of BKCa channels thus serves as a negative feedback mechanism to limit Ca2+ influx in excitable cells. Clotrimazole, an imidazole P-450 inhibitor used for the management of sickle cell anemia, can directly suppress BKCa channel activity. Riluzole, a drug used for the treatment of amyotrophic lateral sclerosis, can directly enhance channel activity in neuroendocrine cells. This effect may explain its inhibitory action on excitatory neurotransmission. 2-Methoxyestradil, an endogenous metabolite of 17 β-estradiol, suppresses BKCa channel activity, whereas resveratrol, a natural phytoalexin present in grapes and wine, directly stimulates BKCa channel activity in vascular endothelial cells. These effects may be responsible for their actions on functional activities of endothelial cells. The fenamates, a family of nonsteroidal anti-inflammatory drugs, are also openers of BKCa channels. Therefore, the modulation of BKCa channel activity in excitable and non-excitable cells can be important for therapeutic interventions.

Original languageEnglish
Pages (from-to)649-661
Number of pages13
JournalCurrent Medicinal Chemistry
Issue number8
Publication statusPublished - 2003 Apr 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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