Mechanisms for monovalent cation-dependent depletion of intracellular Mg2+:Na+-independent Mg2+ pathways in guinea-pig smooth muscle

It has been suggested that magnesium deficiency is correlated with many diseases. (31)P NMR experiments were carried out in order to investigate the effects of Na(+) substitution on Mg(2+) depletion in smooth muscle under divalent cation-free conditions. In the taenia of guinea-pig caeci, the intracellular free Mg(2+) concentration ([Mg(2+)](i)) was estimated from the chemical shifts of (1) the β-ATP peak alone and (2) β- and γ-ATP peaks. Both estimations indicated that [Mg(2+)](i) decreased only very slowly in Mg(2+)-free, Ca(2+)-free solutions in which Na(+) was substituted with large cations such as NMDG (N-methyl-D-glucamine) and choline. Furthermore, the measurements of tension development supported the suggestion of preservation of intracellular Mg(2+) with NMDG substitution. Substituting extracellular Na(+) with the small cation, Li(+), also shifted the β-ATP peak towards a lower frequency, but the frequency shift was significantly less than that seen upon Na(+) substitution with K(+). The estimated [Mg(2+)](i) depletion was, however, comparable with that seen after Na(+) substitution with K(+) using the titration curves of metal-free and Mg(2+)-bound ATP obtained in Li(+)-based model solutions. It was concluded that Mg(2+) rapidly decreases only when small cations were the major electrolyte of the extracellular medium. Na(+) substitutions with NMDG, choline or Li(+) had little effect on intracellular ATP concentration after 100 min treatment.