The role of glycolysis in myocardial calcium control

Because glycolysis is thought to be important for maintenance of cellular ion homeostasis, the aim of the present study was to examine the role of glycolysis in the control of cytosolic calcium ([Ca2+](i)) and cell shortening during conditions of increased calcium influx. Thus, [Ca2+](i) and unloaded cell shortening were measured in fura-2/AM loaded rat ventricular myocytes. All cells were superfused with Tyrode's solution containing glucose and pyruvate (to preserve oxidative metabolism), and glycolysis was inhibited by iodoacetate (IAA, 100 mu M). Calcium influx was increased, secondary to an increase in intracellular sodium, by addition of veratrine (1 mu g/ml), or directly by either elevating [Ca2+](o) from 2 to 5 mM or by exposing the cells to isoproterenol (1 to 100 nM). Veratrine exposure caused a time-dependent increase in both diastolic and systolic [Ca2+](i) that resulted in cellular calcium overload and hypercontraction. The rate of increase in [Ca2+](i) was more rapid in IAA-treated than in untreated myocytes, leading to a 13 +/- 3 v 5 +/- 2% increase (P<0.05) in diastolic [Ca2+](o) after 5 min of exposure. The corresponding increases in systolic [Ca2+](i) were 43 +/- 6 and 24 +/- 5% (P<0.05). Elevated [Ca2+](o) resulted in increased [Ca2+](i) transient amplitudes and cell shortening. These responses were each attenuated by inhibiting glycolysis, so that the increase was 38 +/- 5 v 68 +/- 9% ([Ca2+](i) transient amplitude, P<0.05) and 41 +/- 11 v 91 +/- 18% (cell shortening, P<0.05). Inhibition of glycolysis did not, however, affect the increase in calcium transient or cell shortening during addition of isoproterenol. We conclude that glycolysis plays an essential role in the maintenance of intracellular calcium homeostasis during severe calcium overload. Glycolysis was also essential for signalling the inotropic effect that accompanied elevation in extracellular calcium, while the changes in intracellular calcium following administration of isoproterenol were not influenced by glycolysis in the present model. (C) 1998 Academic Press