Ischaemic Metabolic Factors—High Inorganic Phosphate and Acidosis—Modulate Mitochondrial Creatine Kinase Functional Activity in Skinned Cardiac Fibres

Abstract

Saponin-skinned rat cardiac fibres were used to study the influence of ischaemic factors (high [Pi] and decreased pH) on functional activity of mitochondrial creatine kinase (mi-CK) in situ by evaluation of the stimulation of respiration by creatine. High (20 mM) [Pi] known to solubilize mi-CK, decreased this stimulation significantly, though mi-CK was still present in the mitochondrial compartment. Acidosis (pH 6.6) increased the stimulation of respiration by creatine at low [Pi], and prevented the decreased in mi-CK functional activity at high [Pi]. Thus, these two ischaemic factors act in opposite directions. The data obtained suggest that under physiological or pathological conditions, inorganic phosphate and protons, by changing the functional coupling between creatine kinase and translocase, may influence the distribution of energy fluxes through adenylate and creatine kinase systems in cardiac tissue. Presence of creatine kinase in mitochondrial compartment is not alone sufficient for functional efficacy of the enzyme.