This project focuses on the mechanism whereby cells achieve homeostasis of Ca2+ ion concentration, both within the cytosol and other cellular compartments, and allow changes in Ca2+ in response of hormones and neurotransmitters. This year we have studied the response of intramitochondrial free Ca2+ ([Ca2+]m) to stimulation of isolated, single rat cardiac myocytes, both electrically and by beta-adrenergic agonists. Increasing frequency of electrical stimulation, over the range 0 to 2 Hz, caused modest increases in [Ca2+]m: beta-adrenergic stimulation had no effect on the quiescent cell (mean [Ca2+]m = 75 nM) but caused a marked increase in cells stimulated at 2 Hz (mean [Ca2+]m increased from 120 to 570 nM). Further, when [Ca2+]m was raised in non-electrically stimulated cells, e.g. by partial Na+-replacement, ~-adrenergic stimulation had no effect. Thus, the effect of adrenergic agonists on [Ca2+]m is via changes in systolic transients in Ca2+, rather than on the mitochondrial Ca2+ transport proteins per se. Values of [Ca2+]m in cells stimulated at near- physiological frequencies, viz 4 Hz, are in the range (about 600 nM) giving approximately 50% stimulation of mitochondrial dehydrogenases. This project is a collaboration with the Cardiac Function Section, LCS.
