PMID- 12678784
OWN - NLM
STAT- MEDLINE
DCOM- 20031029
LR  - 20190823
IS  - 0929-8673 (Print)
IS  - 0929-8673 (Linking)
VI  - 10
IP  - 8
DP  - 2003 Apr
TI  - Large-conductance Ca2+- activated K+ channels:physiological role and 
      pharmacology.
PG  - 649-61
AB  - Large-conductance Ca(2+)-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 Ca(2+) or membrane depolarization. 
      These channels, which are widely distributed in a variety of cells, can control 
      Ca(2+) influx as well as a number of Ca(2+)-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 Ca(2+) 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 Ca(2+) 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 
      17beta-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.
FAU - Wu, Sheng-Nan
AU  - Wu SN
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung City, Taiwan. snwu@isca.vghks.gov.tw
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United Arab Emirates
TA  - Curr Med Chem
JT  - Current medicinal chemistry
JID - 9440157
RN  - 0 (Large-Conductance Calcium-Activated Potassium Channels)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Potassium Channels, Calcium-Activated)
SB  - IM
MH  - Animals
MH  - Electrophysiology
MH  - Humans
MH  - Large-Conductance Calcium-Activated Potassium Channels
MH  - Potassium Channel Blockers/*pharmacology
MH  - Potassium Channels, Calcium-Activated/chemistry/*drug effects/*physiology
RF  - 128
EDAT- 2003/04/08 05:00
MHDA- 2003/10/30 05:00
CRDT- 2003/04/08 05:00
PHST- 2003/04/08 05:00 [pubmed]
PHST- 2003/10/30 05:00 [medline]
PHST- 2003/04/08 05:00 [entrez]
AID - 10.2174/0929867033457863 [doi]
PST - ppublish
SO  - Curr Med Chem. 2003 Apr;10(8):649-61. doi: 10.2174/0929867033457863.