Beta-adrenoceptor-mediated depolarization of the resting membrane in guinea-pig papillary muscles: changes in intracellular Na+, K+ and Cl- activities.
Effects of beta-adrenergic stimulation on the membrane potential and intracellular Na+, K+ and Cl- activities were examined in isolated guinea-pig ventricular muscles using conventional and ion-selective electrodes. Isoproterenol in concentrations of 30 nM - 1 microM produced a transient depolarization followed by a slight hyperpolarization in electrically stimulated or quiescent papillary muscles. The negative logarithm of the concentration producing 50% maximum effect (pD2) for the membrane-depolarizing effect of isoproterenol was smaller than that for the positive inotropic effect, suggesting that a higher level of cAMP accumulation is required to produce the transient depolarization. Whereas the isoproterenol(1 microM)-induced depolarization was not blocked by tetrodotoxin (10 microM), nifedipine (10 microM), Cs+ (5 mM), Ba2+ (0.3 mM), amiloride (1 mM) or ouabain (10 microM), it was significantly attenuated by anthracene-9-carboxylic acid (1 mM), a Cl(-)-channel blocker. Intracellular K+ activity increased, whereas intracellular Na+ activity slightly decreased during the transient depolarization. Intracellular Cl- activity significantly decreased during the isoproterenol-induced depolarization of the resting membrane. These results suggest that an inward current resulting from outward Cl- movement, rather than inward Na+ movement, may be involved in the beta-adrenoceptor-mediated membrane depolarization.
Nakaya
H
H
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Hattori
Y
Y
Tohse
N
N
Shida
S
S
Kanno
M
M
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009467:Neuromuscular Depolarizing Agents; D010210:Papillary Muscles / Q000187:drug effects; D011188:Potassium / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D002712:Chlorides; D009467:Neuromuscular Depolarizing Agents; D012964:Sodium; D000242:Cyclic AMP; D007545:Isoproterenol; D011188:Potassium