MODULATION BY CHLORAMINE-T OF 4-AMINOPYRIDINE-SENSITIVE TRANSIENT OUTWARD CURRENT IN RABBIT ATRIAL CELLS

The effects of an oxidizing agent, chloramine-T, on the 4-aminopyridin e-sensitive transient outward current (I-TO) were investigated in rabb it atrial myocytes by using patch-clamp techniques. Extracellular appl ication of chloramine-T at 20 mu M irreversibly slowed the time course of inactivation of the whole-cell I-TO, and increased the peak by 19. 3% (n = 19) at +40 mV. At 100 mu M, chloramine-T decreased the peak by 22.5% (n = 9) of the control, and subsequently induced a glibenclamid e-sensitive time-independent outward K+ current. Under superfusion wit h dithiothreitol (3 mM), chloramine-T (100 mu M) produced no change in I-TO. The chloramine-T-induced slowing of I-TO inactivation was parti ally reversed by subsequent application of 3 mM dithiothreitol. In sin gle-channel recordings with the cell-attached patch configuration, chl oramine-T (20 mu M) increased the open probability of the I-TO channel from 0.15 to 0.46 at a potential 100 mV positive to the resting poten tial, and the mean open lifetime from 5.1 ms to 7.0 ms (n = 5). The un itary current amplitude that: (1) inactivation of the native A-type ch annels of rabbit heart is susceptible to oxidation; and (2) oxidation of I-TO channels may contribute to the genesis of arrhythmias. (C) 199 8 Elsevier Science B.V. All rights reserved.