ROLE OF NA+/H+ EXCHANGE IN THE RECOVERY OF CONTRACTILITY DURING HYPERCAPNIA IN CAT PAPILLARY-MUSCLES

Experiments were performed in cat papillary muscles contracting isometrically at a constant frequency (0.2 Hz) and temperature (29-degrees-C). Contractility was evaluated by developed tension (T) and its first derivative (T over circle). Hypercapnia was induced by switching the perfusate equilibrated with 50% CO2-95% O2 to a solution equilibrated with 12% CO2 - 88% O2. Composition of this second solution was either identical to the first one (pH0 6.90, experiments at variable pH0 vpH) or with a higher [NaHCO3] to keep pH0 constant at 7.4 during the hypercapnic period (experiments at constant pH0, cpH0). The increase in CO,elicited a similar decrease in contractility at cpH0 and vpH0. Minimal mean + T over circle values were 58.5 +/- 2.9% nd 55.4 +/- 3.2% and occurred at 3.6 +/- 0.75 min and 4.5 +/- 1.52 min of hypercapnia, at cpH0 and vpH. respectively. Contractility recovery after the initial fall, was significantly greater when hypercapnia occurred at cpH0. Return to normocapnia elicited an increase in contractility over control values (overshoot). When [Na+]e was decreased by 60%, hypercapnia produced a similar negative inotropic effect than at control [Na+]e but significantly diminished the degree of recovery at either cpH0 or vpH0. Hypercapnic acidosis at cpH0, in the presence of 5 x 10(-6) M ethylisopropylamiloride (EIPA), a specific inhibitor of Na+/H+ exchange, evoked a maximum negative inotropic effect significantly greater than in its absence and suppressed the recovery of contractility. In all cases the magnitude of the overshoot upon return to normocapnia paralleled the magnitude of contractility recovery during hypercapnia. The results suggest that the recovery of contractility during hypercapnic acidosis is entirely depedent upon the Na+/H+exchanger.