Beat-to-beat oscillations of mitochondrial [Ca(2+)] in cardiac cells

The Ca(2+)-sensitive photoprotein aequorin and the new green fluorescent protein-based fluorescent Ca(2+) indicators ‘ratiometric-pericam’ were selectively expressed in the mitochondria, cytosol and/or nucleus of spontaneously beating ventricular myocytes from neonatal rats. This combined strategy reveals that mitochondrial [Ca(2+)] oscillates rapidly and in synchrony with cytosolic and nuclear [Ca(2+)]. The Ca(2+) oscillations were reduced in frequency and/or amplitude by verapamil and carbachol and were enhanced by isoproterenol and elevation of extracellular [Ca(2+)]. An increased frequency and/or amplitude of cytosolic Ca(2+) spikes was rapidly mirrored by similar changes in mitochondrial Ca(2+) spikes and more slowly by elevations of the interspike Ca(2+) levels. The present data unequivocally demonstrate that in cardiac cells mitochondrial [Ca(2+)] oscillates synchronously with cytosolic [Ca(2+)] and that mitochondrial Ca(2+) handling rapidly adapts to inotropic or chronotropic inputs.