AJP - Cell Physiology, Vol 257, Issue 6 C1177-C1181, Copyright © 1989 by American Physiological Society
Isoproterenol activates a chloride current, not the transient outward current, in rabbit ventricular myocytes
R. D. Harvey and J. R. Hume
Department of Physiology, University of Nevada School of Medicine, Reno 89557-0046.
The effects of beta-adrenergic stimulation on the Ca2(+)-insensitive
transient outward current (Ito) in rabbit ventricular myocytes were
examined. Exposure to isoproterenol (ISO; 1 microM) activated a
time-dependent current at positive membrane potentials. To determine
whether this ISO-induced current was associated with Ito, sensitivity to
the K+ channel antagonist, 3,4-diaminopyridine (DAP; 200 microM) was
compared before and after exposure to ISO. The DAP-sensitive current was
not enhanced by ISO, suggesting that the ISO-induced current was not a
component of Ito. Ito and the ISO-induced current could also be dissociated
by changing the membrane holding potential. Positive holding potentials,
which produced significant inactivation of Ito, had little effect on the
ISO-induced membrane current. Furthermore, the ISO-induced current could be
observed when K+ was replaced by Cs+. The reversal potential of the
ISO-induced current agreed with the predicted Cl- equilibrium potential,
and exposure to Cl(-)-free extracellular solutions eliminated the response
to ISO. Therefore, we conclude that ISO does not directly activate Ito in
rabbit ventricular myocytes, but instead, activates a time-independent
chloride current (ICl) similar to that recently described in guinea pig
ventricular myocytes and shown to be regulated by adenylate cyclase (R. D.
Harvey and J. R. Hume. Science Wash. DC 244: 983-985, 1989).
