Ionic mechanisms of excitation-induced regulation of Na+-K+-ATPase mRNA expression in isolated rat EDL muscle.
This study investigated the effects of electrical stimulation on Na(+)-K(+)-ATPase isoform mRNA, with the aim to identify factors modulating Na(+)-K(+)-ATPase mRNA in isolated rat extensor digitorum longus (EDL) muscle. Interventions designed to mimic exercise-induced increases in intracellular Na(+) and Ca(2+) contents and membrane depolarization were examined. Muscles were mounted on force transducers and stimulated with 60-Hz 10-s pulse trains producing tetanic contractions three times at 10-min intervals. Ouabain (1.0 mM, 120 min), veratridine (0.1 mM, 30 min), and monensin (0.1 mM, 30 min) were used to increase intracellular Na(+) content. High extracellular K(+) (13 mM, 60 min) and the Ca(2+) ionophore A-23187 (0.02 mM, 30 min) were used to induce membrane depolarization and elevated intracellular Ca(2+) content, respectively. Muscles were analyzed for Na(+)-K(+)-ATPase alpha(1)-alpha(3) and beta(1)-beta(3) mRNA (real-time RT-PCR). Electrical stimulation had no immediate effect on Na(+)-K(+)-ATPase mRNA; however at 3 h after stimulation, it increased alpha(1), alpha(2), and alpha(3) mRNA by 223, 621, and 892%, respectively (P = 0.010), without changing beta mRNA. Ouabain, veratridine, and monensin increased intracellular Na(+) content by 769, 724, and 598%, respectively (P = 0.001) but did not increase mRNA of any isoform. High intracellular K(+) concentration elevated alpha(1) mRNA by 160% (P = 0.021), whereas A-23187 elevated alpha(3) mRNA by 123% (P = 0.035) but reduced beta(1) mRNA by 76% (P = 0.001). In conclusion, electrical stimulation induced subunit-specific increases in Na(+)-K(+)-ATPase mRNA in isolated rat EDL muscle. Furthermore, Na(+)-K(+)-ATPase mRNA appears to be regulated by different stimuli, including cellular changes associated with membrane depolarization and increased intracellular Ca(2+) content but not increased intracellular Na(+) content.[1]References
- Ionic mechanisms of excitation-induced regulation of Na+-K+-ATPase mRNA expression in isolated rat EDL muscle. Murphy, K.T., Macdonald, W.A., McKenna, M.J., Clausen, T. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
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