Differential pharmacology of the cardiac anionic background current I(AB).
A novel anionic background conductance (I(AB)) in cardiac ventricular myocytes has recently been identified but at present there is comparatively little information on its pharmacological modulation. This study investigated the effects of on I(AB) of four pyrethroid agents tefluthrin (a selective activator of this current), tetramethrin, fenpropathrin and alpha-cypermethrin in addition to other well known chloride channel modulators (chlorotoxin, gadolinium and picrotoxin). Guinea-pig ventricular myocytes were isolated using an enzymatic and mechanical dispersion procedure and all electrophysiological measurements were made using the whole-cell patch-clamp technique. In contrast to other anion conductances (stretch- or volume-regulated chloride current (I(Cl,vol)), a cAMP-dependent Cl(-) current (I(Cl,cAMP))) I(AB) was augmented by tefluthrin, fenpropathrin, alpha-cypermethrin (but not tetramethrin). I(AB) was insensitive to chlorotoxin, gadolinium and picrotoxin. Thus, I(AB) exhibits a distinct pharmacological profile from other known cardiac anion conductances.
Borg
John J
JJ
Department of Pharmacology, School of Medical Sciences, University Walk, University of Bristol, Bristol BS8 1TD, UK. john-joseph.borg@gov.mt
Hancox
Jules C
JC
Zhang
Henggui
H
Spencer
Christopher Ian
CI
Li
Hongyu
H
Kozlowski
Roland Z
RZ
D000818:Animals; D000838:Anions / Q000378:metabolism; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D003521:Cyclopropanes / Q000494:pharmacology; D004553:Electric Conductivity; D004594:Electrophysiology; D005682:Gadolinium / Q000494:pharmacology*; D006168:Guinea Pigs; D006352:Heart Ventricles; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology*; D011722:Pyrethrins / Q000494:pharmacology*; D012604:Scorpion Venoms / Q000494:pharmacology*
D000838:Anions; D018118:Chloride Channels; D000242:Cyclic AMP; D003521:Cyclopropanes; D005682:Gadolinium; D006845:Hydrocarbons, Fluorinated; D010852:Picrotoxin; D011722:Pyrethrins; D012604:Scorpion Venoms; C091539:Chlorotoxin; C017160:cypermethrin; C489827:2,3,5,6-tetrafluoro-4-methylbenzyl (Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate; C044267:fenpropathrin; C009424:tetramethrin