心筋代謝阻害時のNa⁺/Mg²⁺交換輸送活性

抄録

Intracellular free Mg²⁺ concentration ([Mg²⁺]_i) of rat ventricular myocytes were measured with the fluorescent indicator furaptra (mag-fura 2). To estimate the rates of Mg²⁺ efflux by the Na⁺/Mg²⁺ exchange in deenergized cells, we treated the cells with a metabolic inhibitor in the Na⁺ and Ca²⁺-free conditions, and analyzed the initial rate of decrease in [Mg²⁺]_i upon introduction of extracellular Na⁺ at 25°C. Treatment of the cells with 1 μ M FCCP, an uncoupler of mitrochondria, significantly increased [Mg²⁺]_i for 10 min, on average, from 0.94 mM to 2.47 mM (probably due to breakdown of ATP and release of Mg²⁺ from Mg²⁺ATP) and shortened the cell length (probably due to formation of rigor crossbridges). Similar effects were observed after application of 5 mM KCN for 60-90 min. The Mg²⁺ efflux rate was largely reduced, by 78±5.1% (n=6) or 47±15.9% (n=4) in FCCP- or KCN-treated cells, respectively. The slowed Mg²⁺ efflux is unlikely attributed to intracellular acidosis caused by metabolic inhibition, because equilibration of intracellular and extracellular pH at 7.15 by addition of 10 μM nigericin, a proton ionophore, did not reverse the inhibition of the Mg²⁺ efflux. In FCCP-treated cells, the decrease in [Mg²⁺]_i was initially slow (above), but was often markedly accelerated in later periods after variable latency. As the late decrease in [Mg²⁺]_i was observed even in the absence of extracellular Na⁺, this late component seems unrelated to Mg²⁺ efflux by Na⁺/Mg²⁺ exchange. We conclude that Na⁺/Mg²⁺ exchange was largely inhibited by metabolic inhibition, presumably due to depletion of intracellular ATP. [J Physiol Sci. 2007;57 Suppl:S128]