Voltage-dependent stimulation of the Na(+)-K(+) pump by insulin in rabbit cardiac myocytes |
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Authors: | Hansen P S Buhagiar K A Gray D F Rasmussen H H |
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Affiliation: | Department of Cardiology, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia. |
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Abstract: | Insulin enhancesNa+-K+ pump activity in various noncardiactissues. We examined whether insulin exposure in vitro regulates Na+-K+ pump function in rabbit ventricularmyocytes. Pump current (Ip) was measured using thewhole-cell patch-clamp technique at test potentials(Vms) from 100 to +60 mV. When theNa+ concentration in the patch pipette(Na]pip) was 10 mM, insulin caused aVm-dependent increase in Ip.The increase was ~70% when Vm was at nearphysiological diastolic potentials. This effect persisted afterelimination of extracellular voltage-dependent steps and whenK+ and K+-congeners were excluded from thepatch pipettes. When Na]pip was 80 mM, causingnear-maximal pump stimulation, insulin had no effect, suggesting thatit did not cause an increase in membrane pump density. Effects oftyrphostin A25, wortmannin, okadaic acid, or bisindolylmaleimide I inpipette solutions suggested that the insulin-induced increase inIp involved activation of tyrosine kinase,phosphatidylinositol 3-kinase, and protein phosphatase 1, whereasprotein phosphatase 2A and protein kinase C were not involved. |
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