Sustained outward current observed after I(to1) 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 (Isus) remains constant for at least 5 s during continued depolarization. The present study was designed to identify the ionic mechanism underlying Isus 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 Isus was unaffected. Isus 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. Isus 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 Isus showed outward rectification, and the reversal potential of Isus shifted with changes in the transmembrane Cl- gradient in the fashion expected for a Cl- current. We conclude that Isus 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.
Duan
D Y
DY
Department of Medicine, University of Montreal, Quebec, Canada.
Fermini
B
B
Nattel
S
S
D000818:Animals; D002712:Chlorides / Q000502:physiology*; D004553:Electric Conductivity; D004594:Electrophysiology; D006321:Heart / Q000502:physiology*; D006325:Heart Atria; D009206:Myocardium / Q000166:cytology; D011188:Potassium / Q000502:physiology; D011817:Rabbits
D002712:Chlorides; D011188:Potassium