On the mechanism of A23187-induced potassium efflux in rat liver mitochondria.
1. Rat liver mitochondria undergo a spontaneous, respiration-dependent K+ extrusion which is accelerated by citrate. This K+ efflux is electroneutral and is considered to occur on an endogenous K/H exchanger. The spontaneous efflux, but not nigericin-induced K/H exchange, is always preceded by a lag phase, suggesting that the lag phase is a characteristic property of the endogenous exchange reaction. 2. K+ extrusion induced by ionophore A23187 also has the characteristics of K/H exchange. The rate of K+ efflux is faster and the lag time is shorter when compared to endogenous K+ efflux. The effects of A23187 on the lag phase suggest that the ionophore acts by unmasking the endogenous exchanger. This conclusion is supported by the finding that K+ efflux rates reach a maximum which cannot be exceeded by increasing the dose of A23187 but is exceeded by adding nigericin. 3. Steady state perturbation studies were carried out on respiring mitochondria in which electrophoretic K+ influx was balanced by electroneutral K+ efflux. These steady states were appropriately shifted in opposite directions by additions of nigericin or valinomycin. In contrast, addition of A23187 had no effect. It is concluded that A23187 is incapable of transporting K+ in rat liver mitochondria. 4. These results are consistent with a model in which free matrix Mg2+ acts as a K/H carrier "brake." The proposed role of this carrier-brake mechanism is to provide volume homeostasis with minimal energy expenditure. According to this model, both citrate and A23187 stimulate K/H exchange by reducing Mg2+ activity within the matrix. Citrate acts by complexation of Mg2+, while A23187 acts by transporting Mg2+ out of the matrix.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology*; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009550:Nigericin / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D013757:Tetraethylammonium Compounds; D000001:Calcimycin; D008274:Magnesium; D009550:Nigericin; D011188:Potassium