BETA(1) ADRENOCEPTOR-MEDIATED DECREASE IN PH(1) IN QUIESCENT VENTRICULAR VENTRICULAR MYOCARDIUM

Objective: The aims were to examine the effect of beta adrenergic stimulation on the intracellular pH (pH(i)) and to compare it with that of alpha adrenergic stimulation in ventricular myocardium. Methods: Using conventional and ion selective electrodes membrane potential and pH(i) were measured simultaneously in quiescent papillary muscles of guinea pigs in HEPES or bicarbonate buffered solution. Isoprenaline and propranolol (1 muM) plus phenylephrine (30 muM) were used to stimulate beta and alpha adrenoceptors, respectively. In order to evaluate underlying mechanism(s) of beta adrenoceptor mediated pH(i) change, effects of Na+-H+ exchange, Cl--HCO3- exchange, Na+-HCO3- symport, and glycolysis blockers on the pH(i) change were examined. Results: Isoprenaline (1 muM) produced a decrease in pH(i) of 0.08(SEM. 0.01) pH units and a transient depolarisation of the resting membrane. The isoprenaline induced intracellular acidosis was blocked by the beta1 blocker atenolol (10 muM) but not by the beta2 blocker ICI 118,551 (0.1 muM). Forskolin also produced a decrease in pH(i) of 0.06(0.03) pH units. In contrast, alpha adrenergic stimulation produced an increase in pH(i), which was abolished by 1 mM amiloride, an Na+-H+ exchange blocker. In the presence of amiloride, the isoprenaline induced decrease in pH(i) was rather enhanced. 4,4'-Diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS, 1 mM), a blocker of Cl--HCO3 exchange and the Na+-HCO3- symport system, failed to affect the isoprenaline induced pH(i) decrease in bicarbonate buffered solution. However, pretreatment with 2-deoxyglucose or iodoacetic acid abolished the isoprenaline induced pH(i) decrease. Conclusions: beta1 Adrenoceptor stimulation causes- intracellular acidosis via the enhanced glycolysis, and the Na+-H+ exchange system appears to play a compensatory role. The beta1 adrenoceptor mediated intracellular acidosis may modulate inotropic response to adrenergic stimulation in ventricular myocardium.