Mechanisms of Na+-K+pump regulation in cardiac myocytes during hyposmolar swelling
| Autor: | Clyne Fernandes, Nerida L. Bewick, Helge H. Rasmussen, A. D. Pitt, David Whalley |
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| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty Patch-Clamp Techniques Physiology Morpholines Membrane Potentials Phosphatidylinositol 3-Kinases Protein Phosphatase 1 Internal medicine Okadaic Acid Phosphoprotein Phosphatases medicine Animals Homeostasis Myocyte Patch clamp Enzyme Inhibitors Na+/K+-ATPase Protein Kinase C Ion transporter Cell Size Phosphoinositide-3 Kinase Inhibitors Sarcolemma Chemistry Myocardium Cell Biology Protein-Tyrosine Kinases Tyrphostins Membrane transport Endocrinology Hypotonic Solutions Chromones Biophysics Tonicity Calcium Rabbits Sodium-Potassium-Exchanging ATPase |
| Zdroj: | American Journal of Physiology-Cell Physiology. 276:C1091-C1099 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.1999.276.5.c1091 |
| Popis: | We have previously demonstrated that the sarcolemmal Na+-K+pump current ( Ip) in cardiac myocytes is stimulated by cell swelling induced by exposure to hyposmolar solutions. However, the underlying mechanism has not been examined. Because cell swelling activates stretch-sensitive ion channels and intracellular messenger pathways, we examined their role in mediating Ipstimulation during exposure of rabbit ventricular myocytes to a hyposmolar solution. Ipwas measured by the whole cell patch-clamp technique. Swelling-induced pump stimulation altered the voltage dependence of Ip. Pump stimulation persisted in the absence of extracellular Na+and under conditions designed to minimize changes in intracellular Ca2+, excluding an indirect influence on Ipmediated via fluxes through stretch-activated channels. Pump stimulation was protein kinase C independent. The tyrosine kinase inhibitor tyrphostin A25, the phosphatidylinositol 3-kinase inhibitor LY-294002, and the protein phosphatase-1 and -2A inhibitor okadaic acid abolished Ipstimulation. Our findings suggest that swelling-induced pump stimulation involves the activation of tyrosine kinase, phosphatidylinositol 3-kinase, and a serine/threonine protein phosphatase. Activation of this messenger cascade may cause activation by the dephosphorylation of pump units. |
| Databáze: | OpenAIRE |
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