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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 pHi, 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. pHi was recorded fluorimetrically with acetoxymethyl (AM)-loaded carboxy-SNARF-1 at either 27 or 37 degrees C. At 27 degrees C, intrinsic (non-CO2-dependent) buffering power (betai) was approximately 60% of that at 37 degrees C. Acid-extrusion (Je) through NHE was approximately 50% slower than at 37 degrees C, consistent with a Q10 of approximately 2. In 5% CO2/HCO3--buffered conditions, in the presence of 30 microM cariporide to inhibit NHE, acid extrusion via NBC was also slowed at 27 degrees C, suggestive of a comparable Q10. Resting pHi at 27 degrees C was similar in Hepes- or 5% CO2/HCO3--buffered superfusates but, in both cases, was approximately 0.1 pH units lower at 37 degrees C. The higher the starting pHi, the larger was the thermally induced fall of pHi, consistent with a mathematical model where intrinsic buffers with a low principal pKa (e.g. close to 6.0) are less temperature-sensitive than those with a higher pKa. The high temperature sensitivity of pHi 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.

Original publication

DOI

10.1113/jphysiol.2003.051888

Type

Journal article

Journal

J Physiol

Publication Date

01/11/2003

Volume

552

Pages

715 - 726

Keywords

Animals, Benzopyrans, Buffers, Fluorescent Dyes, Guinea Pigs, Heart Ventricles, Hydrogen-Ion Concentration, Intracellular Fluid, Myocytes, Cardiac, Naphthols, Protons, Rhodamines, Sodium-Bicarbonate Symporters, Sodium-Hydrogen Antiporter, Temperature