The sodium ion/calcium ion cycle of cardiac mitochondria.

A number of advances have been made recently in our knowledge of the mechanisms of mitochondrial Ca2+ transport, and these offer new perspectives to the problem of why mitochondria transport Cal+. Progress with cardiac mitochondria has been favoured by the resolution of the overall flux of Caz+ across the inner membrane into two distinct components, which represent catalysis by two separate carriers (Crompton & Carafoli, 1979). Ca'+ accumulation is catalysed by a specific carrier, which may be inhibited by very low amounts of Ruthenium Red and lanthanides (Mela, 1969; Moore, 1971; Reed & Bygrave, 1974), of which the best are the smaller lanthanides, Tm3+ to Sm3+ (Crompton et al., 1979a). In cardiac mitochondria, the latter yield 5096 inhibition with 1.5 pmol of lanthanide/mg of mitochondrial protein, which indicates that these mitochondria contain less than 3 pmol of La3+-sensitive sites on the carrier per mg of protein. Reed & Bygrave (1974) provided a similar value for liver mitochondria. In cardiac mitochondria, the velocity of Ca2+ influx is directly proportional to the inner membrane potential, with a value of 80pmol of Ca2+.mg of protein-l-s-l.mV-l at 37OC (M. Crompton, unpublished work). One may therefore calculate a single channel flux of at least 27s-'.mV-'. At a membrane potential of 15&200mV, which is assumed to be physiological (Mitchell & Moyle, 1969; Nicholls, 1974), the flux becomes 4000-5000s-'. When, specifically, Na+ is excluded from the medium (for reasons stated below), the transport reaction approaches equilibrium and, under these conditions, the gradient in electrochemical potential of Ca*+ across the inner membrane becomes zero within experimental error over a wide range of values of the membrane potential (Crompton & Heid, 1978). It seems, therefore, that the carrier is a uniporter, which catalyses the movement of Cal+ down its gradient of electrochemical