[Beta 1-adrenoceptor-mediated changes in intracellular Na+, K+, Cl- activities and pHi in guinea-pig ventricular...

Effects of beta-adrenergic stimulation on the membrane potential and intracellular Na+, K+, Cl- activities and pH (pHi) were examined in isolated guinea-pig ventricular muscles using conventional and ion-selective microelectrodes. Isoproterenol (1 microM) produced a transient membrane depolarization followed by a slight hyperpolarization in quiescent papillary muscles. Although 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 (9 AC, 1 mM), a Cl(-)-channel blocker. Intracellular K+ activity increased, whereas intracellular Na+ activity slightly decreased during beta-adrenergic stimulation. Intracellular Cl- activity significantly decreased during the isoproterenol-induced depolarization of the resting membrane potential, which was attenuated by 9 AC. Isoproterenol significantly decreased pHi, which was enhanced by amiloride. 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid(DIDS, 1 mM), a stilbene derivative possessing blocking action on Cl-/HCO3- exchange system and Na+/HCO3- symport system, failed to affect the isoproterenol-induced acidosis, but pretreatment with 2-deoxyglucose (2-DG, 5.5 mM) or iodoacetic acid(IAA, 0.3 mM) abolished the isoproterenol-induced pHi decrease. Thus, beta-adrenergic stimulation decreased aiCl, aiNa and pHi, and increased aiK. The decrease in aiCl may be ascribed to the activation of Cl- channels, and opposite changes in aiNa and aiK appear to be due to the beta-adrenoceptor mediated activation of Na+/K+ pump. Acceleration of glycolysis during beta-adrenergic stimulation may be responsible for the intracellular acidosis. These changes in intracellular ionic activities may play a role in the modulation of electromechanical response to beta-adrenergic stimulation.