Specific up-regulation of mitochondrial F0F1-ATPase activity after short episodes of atrial fibrillation in sheep

ATPase Activity and Atrial Fibrillation. Introduction: Ventricular fibrillation induced by either digitalis intoxication or electrical stimulation is reported to alter myocardial energy by impairing the sarcolemmal Na,K-ATPase or the receptor for digitalis and the mitochondrial ATPase synthase or F0F1-ATPase. However, little is known about these membrane functions during atrial fibrillation (AF). Methods and Results: We analyzed the effects of electrically induced AF on biochemical activities of atrial F0F1-ATPase and Na,K-ATPase in sheep. A group of six sheep was subjected to direct short electrical stimulation of the right atrium to induce AF. Sham-operated sheep served as a control group. Microsomal and mitochondrial membranes of atrial muscle were isolated and tested for enzymatic activity. All paced sheep developed multiple episodes of sustained AF, with a mean total duration of 110 minutes over a 2-hour period. Data showed that short-term pacing-induced AF significantly activated membrane F0F1-ATPase artivity (P < 0.05) without changes in cytochrome-c oxidase activity, Na,K-TPase activity, ouabain sensitivity, and alpha(1)-subunit expression, Conclusion: Specific activation of F0F1-ATPase activity is an early molecular consequence of sustained AF in sheep.