The regulation of intracellular pH in the diabetic myocardium

Time for primary review 25 days. . In myocardial cells, as in any given cell, steady-state intracellular pH (pHi) is strictly maintained within a narrow range at relatively alkaline values. Resting pHi (7.1–7.2) is determined by the algebraic sum of acid-loading and acid-extruding processes. Whenever acid-loading exceeds acid extrusion, pHi falls. The degree to which pHi changes is inversely related to the intracellular buffering power (βi). The role of intracellular buffering power, which is the first line of defence of a cardiac cell against an intracellular acid–base disturbance, is to moderate pHi changes produced by acute acid (or alkali) load [1]. However, buffering mechanisms cannot prevent a change in pHi, but only reduce its amplitude. The regulation of pHi then largely depends upon the activity of plasma membrane carrier-mediated transport of acid/base equivalents [2, 3]. Intracellular pH is important for the activity of a number of enzymes with optimal pH within the physiological pH range, as well as for the conductivity of ion channels [4], calcium homeostasis, and the efficiency of contractile elements [5, 6]. Despite a vast literature demonstrating myocardial metabolic changes associated with diabetes (for reviews, see Refs. [7, 8]), until recent years relatively few studies have addressed the effects of diabetes on intracellular pH. Yet, disturbances in intracellular pH or in the processes regulating intracellular pH may be expected to occur in diabetic hearts as a result of either altered cellular metabolism and/or cellular and subcellular membrane changes. This review provides a summary of the data obtained with both multicellular and single cell preparations, as well as with isolated hearts from chemically-induced diabetic rats. The first study that allowed direct measurement of intracellular pH in cardiac cells of streptozotocin (STZ)-induced diabetic rat hearts was … * Tel.: +33 (1) 69 15 78 98; fax: +33 (1) 69 15 68 41.