The isoproterenol-induced chloride current and cardiac resting potential.
Isoproterenol can induce potentially arrhymthogenic depolarizations of the resting membrane of single guinea-pig ventricular myocytes. This effect on resting potential of single guinea-pig ventricular myocytes differs qualitatively from results obtained by others from intact cardiac muscle preparations and also differs from our experience with single dog ventricular myocytes. We performed experiments on dog and guinea-pig ventricular myocytes in an attempt to clarify the effects of isoproterenol on the resting potential of mammalian ventricular myocytes. Voltage recordings with 40-60 M omega 3 M potassium chloride filled microelectrodes revealed an isoproterenol-induced depolarization of 4.3 +/- 1.0 mV in guinea-pig but no depolarization in dog myocytes. Activation of an outwardly rectifying chloride current is responsible for the isoproterenol-induced depolarization of guinea-pig ventricular myocytes. Our whole cell patch clamp recordings consistently revealed such a current in guinea-pig cells but always failed to demonstrate an isoproterenol-induced chloride current in dog myocytes under identical conditions. In contrast to single cells, isoproterenol did not depolarize intact guinea-pig papillary muscle when potential was recorded with 40-60 M omega 3 M KCl filled electrodes. Furthermore, we saw no depolarization in single guinea-pig myocytes when recording electrodes did not contain chloride. We conclude that: (1) despite activation of a chloride current, isoproterenol does not significantly depolarize guinea-pig ventricular muscle unless the driving force for the current at the resting potential is increased by elevating [Cl]i above physiological levels, and (2) an isoproterenol-induced chloride current, although demonstrable in guinea-pig ventricular cells, is not present in healthy dog ventricular cells.
Sorota
S
S
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Siegal
M S
MS
Hoffman
B F
BF
D000818:Animals; D001693:Biological Transport, Active; D002712:Chlorides / Q000378:metabolism*; D003217:Conductometry; D004285:Dogs; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology*; D007545:Isoproterenol / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*
D002712:Chlorides; D007545:Isoproterenol