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Am J Physiol Cell Physiol 278: C546-C553, 2000;
0363-6143/00 $5.00
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Vol. 278, Issue 3, C546-C553, March 2000

Voltage-dependent stimulation of the Na+-K+ pump by insulin in rabbit cardiac myocytes

Peter S. Hansen, Kerrie A. Buhagiar, David F. Gray, and Helge H. Rasmussen

Department of Cardiology, Royal North Shore Hospital, and Department of Medicine, University of Sydney, St. Leonards, New South Wales 2065, Australia

Insulin enhances Na+-K+ pump activity in various noncardiac tissues. We examined whether insulin exposure in vitro regulates Na+-K+ pump function in rabbit ventricular myocytes. Pump current (Ip) was measured using the whole-cell patch-clamp technique at test potentials (Vms) from -100 to +60 mV. When the Na+ concentration in the patch pipette ([Na]pip) was 10 mM, insulin caused a Vm-dependent increase in Ip. The increase was ~70% when Vm was at near physiological diastolic potentials. This effect persisted after elimination of extracellular voltage-dependent steps and when K+ and K+-congeners were excluded from the patch pipettes. When [Na]pip was 80 mM, causing near-maximal pump stimulation, insulin had no effect, suggesting that it did not cause an increase in membrane pump density. Effects of tyrphostin A25, wortmannin, okadaic acid, or bisindolylmaleimide I in pipette solutions suggested that the insulin-induced increase in Ip involved activation of tyrosine kinase, phosphatidylinositol 3-kinase, and protein phosphatase 1, whereas protein phosphatase 2A and protein kinase C were not involved.

sodium-potassium-adenosinetriphosphatase; whole-cell voltage clamp; second messengers


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