Overlapping pharmacology of Ca2+-activated Cl- and K+ channels.
Research into Ca2+-activated Cl- channels is hampered by the inability to decipher their molecular identity and the fact that all extant Cl- channel blockers have effects on other ion channels. Most notably, Cl- channel blockers such as the fenamates (e.g. niflumic acid and flufenamic acid) activate Ca2+-dependent K+ channels, although other pharmacological overlaps have been discovered. In this article, we highlight the complex pharmacology of Ca2+-activated Cl- channels and the caveats associated with using these blockers--a necessary requirement because many researchers use Cl- channel blockers as probes for Cl- channel activity. Moreover, we discuss the argument for a common structural motif between Ca2+-activated Cl- channels and Ca2+-dependent K+ channels, which has led to the possibility that the molecular identity of Cl- channels will be revealed by research in this new direction, in addition to the use of existing candidates such as the CLCA, Bestrophin and tweety genes.
Greenwood
Iain A
IA
Ion Channels and Cell Signalling Research Centre, Division of Basic Medical Sciences, St George's, University of London, London SW17 0RE, UK. i.greenwood@sgul.ac.uk
Leblanc
Normand
N
D000818:Animals; D002626:Chemistry, Pharmaceutical; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation
D018118:Chloride Channels; D024681:Potassium Channels, Calcium-Activated