Skip to main content

Large-Conductance Ca2+-Activated K+ Channels:Physiological Role and Pharmacology

Buy Article:

$63.00 plus tax (Refund Policy)


Large-conductance Ca2+-activated K+ (BK-Ca) 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, BK-Ca channels are believed to play an important role in controlling hormonal secretion by altering the duration and frequency of action potentials. The activity of BK-Ca 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 BK-Ca channel activity. Epoxyeicosatrienoic acids, a metabolite of arachidonic acid, and the increase in intracellular cyclic GMP with vinpocetine or YC-1 can stimulate BK-Ca channel activity. The increased activity of BK-Ca 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 BK-Ca 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 17β-estradiol, suppresses BK-Ca channel activity, whereas resveratrol, a natural phytoalexin present in grapes and wine, directly stimulates BK-Ca 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 BK-Ca channels. Therefore, the modulation of BK-Ca channel activity in excitable and non-excitable cells can be important for therapeutic interventions.

Keywords: channel inhibitor; channel opener; intracellular; large-conductance; membrane potential

Document Type: Review Article


Publication date: April 1, 2003

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Partial Open Access Content
Partial Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more