2,4-dinitrophenol acutely inhibits rabbit atrial Ca2+-sensitive Cl- current (ITO2)

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Abstract
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 (ITO2). Amphotericin B perforated-patch, whole-cell patch-clamp technique was employed (35°C) using enzymatically isolated single rabbit atrial myocytes. We defined ITO2 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 ITO2 by ~70% (n = 13). Within 30 s after application of 0.2 mM DNP, both normal ITO2 transients (n = 8) and the ITO2 transients that remained after A9C treatment (n = 8) were inhibited completely. In cells expressing ITO2 (70% of total), DNP also suppressed an A9C-insensitive slow outward current by ~40%, but the holding current at -80 mV was unaffected. There was a ~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 ITO2 via a mechanism presumably separate from metabolic inhibition.Key words: patch clamp, rabbit heart, simulated ischemia, calcium-sensitive chloride current.

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