EFFECTS OF ADRENERGIC AGONISTS AND MITOCHONDRIAL ENERGY-STATE ON THE CA2+ TRANSPORT-SYSTEMS OF MITOCHONDRIA

This study investigates the effects of adrenergic agonists and mitochondrial energy state on the activities of the Ca2+ transport systems of female rat liver mitochondria. Tissue perfusion with the .alpha.-adrenergic agonist phenylephrine and with adrenaline, but not with the .beta.-adrenergic agonist isoprenaline, induced significant activation of the uniporter and the respiratory chain. Uniporter activation was evident under two sets of experimental conditions that excluded influences of .DELTA..psi., i.e., at high .DELTA..psi., where uniporter activity was .DELTA..psi. independent, and at low .DELTA..psi. where uniporter conductance was measured. Preincubation of mitochrondria with extracts from phenylephrine-perfused tissue quantitatively reproduced uniporter activation when comparison was made with mitochondria treated similarly with extracts from tissue perfused without agonist. Similar, but more extensive, data were obtained with heart mitochondria pretreated with extracts from hearts perfused with the .alpha.-adrenergic agonist methoxamine. Phenylephrine did not affect Ca2+ efflux mediated by the Na+-Ca2+ carrier or the Na+-independent system. In contrast, the liver mitochondrial Na+-Ca2+ carrier was activated by tissue perfusion with isoprenaline; the Na+-independent system was unaffected. Na+-Ca2+ carrier activation was not associated with any change in a number of basic bioenergetic parameters. It is concluded that the Ca2+ transport systems of liver mitochondria may be controlled in an opposing manner by .alpha.-adrenergic agonists (promotion of Ca2+ influx) and .beta.-adrenergic agonists (promotion of Ca2+ efflux). At .DELTA..psi. values > 110 mV, the Na+-independent system was activated by increase in .DELTA..psi. the uniporter and Na+-Ca2+ carrier activities were insensitive to .DELTA..psi. changes in this range. In consequence, decreased .DELTA..psi. induced net Ca2+ uptake during steady-state Ca2+ cycling. This offers a further potential mechanism whereby liver mitochondrial Ca2+ and Ca2+-sensitive oxidative metabolism may be autoregulated by the mitochondrial energy state.