Mechanisms of Na+-K+ pump regulation in cardiac myocytes during hyposmolar swelling |
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Authors: | Bewick, N. L. Fernandes, C. Pitt, A. D. Rasmussen, H. H. Whalley, D. W. |
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Abstract: | We have previously demonstrated that the sarcolemmalNa+-K+pump current(Ip) in cardiacmyocytes is stimulated by cell swelling induced by exposure tohyposmolar solutions. However, the underlying mechanism has not beenexamined. Because cell swelling activates stretch-sensitive ionchannels and intracellular messenger pathways, we examined their rolein mediating Ipstimulation during exposure of rabbit ventricular myocytes to ahyposmolar solution.Ip was measuredby the whole cell patch-clamp technique. Swelling-induced pumpstimulation altered the voltage dependence ofIp. Pumpstimulation persisted in the absence of extracellularNa+ and under conditions designedto minimize changes in intracellular Ca2+, excluding an indirectinfluence on Ipmediated via fluxes through stretch-activated channels. Pumpstimulation was protein kinase C independent. The tyrosine kinaseinhibitor tyrphostin A25, the phosphatidylinositol 3-kinase inhibitorLY-294002, and the protein phosphatase-1 and -2A inhibitor okadaic acidabolished Ipstimulation. Our findings suggest that swelling-induced pumpstimulation involves the activation of tyrosine kinase,phosphatidylinositol 3-kinase, and a serine/threonine proteinphosphatase. Activation of this messenger cascade maycause activation by the dephosphorylation of pump units. |
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