Nakayama S, Nomura H, Tomita T
University Department of Pharmacology, Oxford, UK.
J Gen Physiol. 1994 May;103(5):833-51. doi: 10.1085/jgp.103.5.833.
This study is concerned with the regulation of intracellular-free Mg2+ concentration ([Mg2+]i) in the smooth muscle of guinea pig taenia caeci. To assess an interaction of Ca2+ on the Na(+)-dependent Mg(2+)-extrusion mechanism (Na(+)-Mg2+ exchange), effects of Na+ removal (N-methyl-D-glucamine substitution) were examined in Ca(2+)-containing solutions. As changes in pHi in Na(+)-free solutions perturb estimation of [Mg2+]i using the single chemical shift only of the beta-ATP peak in 31P NMR (nuclear magnetic resonance) spectra, [Mg2+]i and pHi were concomitantly estimated from the chemical shifts of the gamma- and beta-peaks. When extracellular Na+ was substituted with N-methyl-D-glucamine, [Mg2+]i was reversibly increased. This increase in [Mg2+]i was eliminated in Mg(2+)-free solutions and enhanced in excess Mg2+ solutions. ATP content fluctuated little during removal and readmission of Na+, indicating that [Mg2+]i changes were not induced by Mg2+ release from ATP, and that Mg(2+)-extruding system would not be inhibited by fuel restriction. A slow acidification in Na(+)-free solutions and transient alkalosis by a readmission of Na+ were observed regardless of the extracellular Mg2+ concentration. When the extracellular Ca2+ concentration was increased from normal (2.4 mM) to 12 mM, only a marginal increase in [Mg2+]i was caused by Na+ removal, whereas a similar slow acidosis was observed, indicating that extracellular Ca2+ inhibits Mg2+ entry, and that the increase in [Mg2+]i is negligible through competition between Mg2+ and Ca2+ in intracellular sites. These results imply that Na(+)-Mg2+ exchange is the main mechanism to maintain low [Mg2+]i even under physiological conditions.
本研究关注豚鼠盲肠带平滑肌细胞内游离镁离子浓度([Mg2+]i)的调节。为评估钙离子对钠依赖性镁离子外排机制(钠-镁离子交换)的影响,在含钙溶液中检测了去除钠离子(用N-甲基-D-葡萄糖胺替代)的效果。由于无钠溶液中细胞内pH值的变化会干扰仅利用31P核磁共振(NMR)谱中β-ATP峰的单一化学位移来估算[Mg2+]i,因此同时根据γ-和β-峰的化学位移估算[Mg2+]i和细胞内pH值。当细胞外钠离子被N-甲基-D-葡萄糖胺替代时,[Mg2+]i可逆性升高。在无镁溶液中,[Mg2+]i的这种升高被消除,而在过量镁离子溶液中则增强。在去除和重新引入钠离子的过程中,ATP含量波动很小,这表明[Mg2+]i的变化不是由ATP释放镁离子引起的,并且镁离子外排系统不会因能量供应受限而受到抑制。无论细胞外镁离子浓度如何,在无钠溶液中均观察到缓慢酸化,重新引入钠离子时则出现短暂碱中毒。当细胞外钙离子浓度从正常的2.4 mM增加到12 mM时,去除钠离子仅引起[Mg2+]i略有升高,同时观察到类似的缓慢酸中毒,这表明细胞外钙离子抑制镁离子内流,并且通过镁离子与钙离子在细胞内位点的竞争,[Mg2+]i的升高可以忽略不计。这些结果表明,即使在生理条件下,钠-镁离子交换也是维持低[Mg2+]i的主要机制。