2,4-dinitrophenol acutely inhibits rabbit atrial Ca2+ -sensitive Cl- current (I(TO2)).
We investigated the effects of 2,4-dinitrophenol (DNP), the uncoupler of mitochondrial oxidative phosphorylation, on the Ca2+ -sensitive Cl- current component of the transient outward current (I(TO2)). Amphotericin B perforated-patch, whole-cell patch-clamp technique was employed (35 degrees C) using enzymatically isolated single rabbit atrial myocytes. We defined I(TO2) as the amplitude of the 2 mM 4-aminopyridine resistant transient outward current sensitive to anthracene-9-carboxylic acid (A9C). Between +5 and +45 mV, 0.2 mM A9C inhibited I(TO2) by approximately 70% (n = 13). Within 30 s after application of 0.2 mM DNP, both normal I(TO2) transients (n = 8) and the I(TO2) transients that remained after A9C treatment (n = 8) were inhibited completely. In cells expressing I(TO2) (70% of total), DNP also suppressed an A9C-insensitive slow outward current by approximately 40%, but the holding current at -80 mV was unaffected. There was a approximately 2 min latency between inhibitory effects of DNP and subsequent membrane current increase, presumably caused by activation of the ATP-sensitive K+ channels (n = 16). We conclude that DNP acutely inhibits I(TO2) via a mechanism presumably separate from metabolic inhibition.
Ravesloot
J H
JH
Department of Physiology, Academic Medical Center, University of Amsterdam, The Netherlands. j.h.ravesloot@amc.uva.nl
Rombouts
E
E
D019297:2,4-Dinitrophenol / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D018118:Chloride Channels / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects; D008297:Male; D011817:Rabbits; D014475:Uncoupling Agents / Q000494:pharmacology*
D018118:Chloride Channels; D014475:Uncoupling Agents; D000255:Adenosine Triphosphate; D019297:2,4-Dinitrophenol; D002118:Calcium