Control of Ca2+ influx and efflux in liver mitochondria.

adrenal cortex and brown adipose tissue: Crompton et al., 1978; Nicholls, 1978; Al-Shaikhaly et al., 1979), the fluxes of Ca2+, Na+ and H+ may be integrated into a cycle (Fig. l), for which evidence has been published (Crompton el al., 1976; Crompton & Heid, 1978; Nicholls & Scott, 1980). In cardiac muscle the cycle would never reach steady state, as it does in vitro, since the [Caz+] in the cytosol oscillates, and these oscillations will be transmitted, although severely damped, via the cycle into a ripple of intramitochondrial [Ca2+l, the mean value of which may change according to the physiological state. Since the uniport reaction is far from equilibrium, it is essentially unaffected by changes in intramitochondrial [Ca2+l. Therefore, fine control of the matrix free [Ca2+l requires that changes in this affect the activity of the Na+/Ca2+ antiporter. This condition is satisfied most simply if the matrix free [Ca2+l is insufficiently high to saturate the antiporter, so that its activity depends directly on the matrix free [Ca2+l. The K, value of the antiporter for Sr2+ ( 2 4 ~ ~ ) suggests that this may be the case, when considered within the context of recent evidence for the regulation of certain dehydrogenases of the citric acid cycle by changes in the intramitochondrial free [Ca2+l over the range 0.l-lOp~ (Denton & McCormack, 1980). Thus one function of the Na+/Ca2+ cycle may be to control the matrix free [Ca2+l in accordance with the regulatory requirements of the dehydrogenases. Al-Shaikhaly, M. H. M., Ncdcrgaard, J. & Cannon, B. (1979) Proc. Natl. Acad. Scl. USA. 76,235s-2355 Crompton, M. & Carafoli, E. (1979) in Detectlon and Measurement cf Free Calcium Ions In Cells (Ashley, C. C. & Campbell, A. K., eds.), ElsevierhIorth-Holland, Amsterdam, in the press Crompton, M. & Heid, I. (1978) Eur. 1. Blochem. 91,599-608 Crompton, M., Capano, M. & Carafoli, E. (1976) Eur. J. Blochem. 69.