Temperature dependence of Na+-H+ exchange, Na+-HCO3- co-transport, intracellular buffering and intracellular pH in guinea-pig ventricular myocytes

Almost all aspects of cardiac function are sensitive to modest changes of temperature. We have examined the thermal sensitivity of intracellular pH regulation in the heart. To do this we determined the temperature sensitivity of pH(i), intracellular buffering capacity, and the activity of sarcolemmal acid-extrusion proteins, Na+-H+ exchange (NHE) and Na+-HCO3- co-transport (NBC) in guinea-pig isolated ventricular myocytes. pH(i) was recorded fluorimetrically with acetoxymethyl (AM)-loaded carboxy-SNARF-1 at either 27 or 37degreesC. At 27degreesC, intrinsic (non-CO2,dependent) buffering power (beta(i)) was similar to60 % of that at 37degreesC. Acid-extrusion (J(e)) through NHE was similar to50 % slower than at 37degreesC, consistent with a Q(10) of similar to2. In 5 % CO2/HCO3--buffered conditions, in the presence of 30 muM cariporide to inhibit NHE, acid extrusion via NBC was also slowed at 27degreesC, suggestive of a comparable Q(10). Resting pH(i) at 27degreesC was similar in Hepes- or 5 % CO2/HCO3 buffered superfusates but, in both cases, was similar to0.1 pH units lower at 37degreesC. The higher the starting pH(i), the larger was the thermally induced fall of pH(i), consistent with a mathematical model where intrinsic buffers with a low principal pK(a) (e.g. close to 6.0) are less temperature-sensitive than those with a higher pK(a). The high temperature sensitivity of pH(i) regulation in mammalian cardiac cells has implications for experimental work conducted at room temperature. It also has implications for the ability of intracellular acidosis to generate intracellular Na+ and Ca2+ overload, cardiac injury and arrhythmia in the heart.