Beat-to-beat oscillations of mitochondrial [Ca2+] in cardiac cells

The Ca2+-sensitive photoprotein aequorin and the new green fluorescent prot ein-based fluorescent Ca2+ indicators 'ratiometric-pericam' were selectivel y expressed in the mitochondria, cytosol and/or nucleus of spontaneously be ating ventricular myocytes from neonatal rats. This combined strategy revea ls that mitochondrial [Ca2+] oscillates rapidly and in synchrony with cytos olic and nuclear [Ca2+]. The Ca2+ oscillations were reduced in frequency an d/or amplitude by verapamil and carbachol and were enhanced by isoprotereno l and elevation of extracellular [Ca2+]. An increased frequency and/or ampl itude of cytosolic Ca2+ spikes was rapidly mirrored by similar changes in m itochondrial Ca2+ spikes and more slowly by elevations of the interspike Ca 2+ levels. The present data unequivocally demonstrate that in cardiac cells mitochondrial [Ca2+] oscillates synchronously with cytosolic [Ca2+] and th at mitochondrial Ca2+ handling rapidly adapts to inotropic or chronotropic inputs.