SUSTAINED OUTWARD CURRENT OBSERVED AFTER ITO1 INACTIVATION IN RABBIT ATRIAL MYOCYTES IS A NOVEL CL- CURRENT

In rabbit atrial myocytes, depolarization of the membrane results in a rapidly activating transient outward current (I(to)) that then decays to a sustained level. The sustained current (I(sus)) remains constant for at least 5 s during continued depolarization. The present study was designed to identify the ionic mechanism underlying I(sus) with the use of whole cell voltage-clamp techniques. After exposure to 2 mM 4-aminopyridine (4-AP), the 4-AP-sensitive transient outward current (I(to1)) was abolished, but I(sus) was unaffected. I(sus) was not blocked by the K+ channel blockers tetraethylammonium chloride and Ba2+, was not changed by increasing superfusate K+ concentration, and was still present when K+ was replaced by Cs+ in both the superfusate and the pipette. I(sus) was significantly reduced by the Cl- transport blockers 4-acetamido-4'-isothiocyanatostilbene-2.2'-disulfonic acid and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. The current-voltage relations of I(sus) showed outward rectification, and the reversal potential of I(sus) shifted with changes in the transmembrane Cl- gradient in the fashion expected for a Cl- current. We conclude that I(sus) in rabbit atrium is due to a noninactivating Cl- current which, unlike previously described cardiac Cl- currents, is manifest in the absence of exogenous stimulators of adenosine 3',5'-cyclic monophosphate formation, cytosolic Ca2+ transients, or cell swelling.