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

Abstract

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 (I(p)) was measured using the whole-cell patch-clamp technique at test potentials (V(m)s) from -100 to +60 mV. When the Na(+) concentration in the patch pipette ([Na](pip)) was 10 mM, insulin caused a V(m)-dependent increase in I(p). The increase was approximately 70% when V(m) 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 I(p) involved activation of tyrosine kinase, phosphatidylinositol 3-kinase, and protein phosphatase 1, whereas protein phosphatase 2A and protein kinase C were not involved.

Apoptotic insults impair Na+, K+-ATPase activity as a mechanism of neuronal death mediated by concurrent ATP deficiency and oxidant stress

“…The effect of strophanthidin was reversible and concentration-dependent with an IC50 of 76 µM. At 500 µM, strophanthidin triggered an Ipump of 29.37±1.70 pA (n=56 cells); the current density was 0.39±0.03 pA/pF, which is comparable to that reported in other neurons, cardiac myocytes, and epithelial cells (Gao et al, 1995;Senatorov et al, 1997;Gao et al, 2000;Hansen et al, 2000). The pump current had an estimated reversal potential of -133 mV, consistent with the voltage-dependent nature of the pump; the reversal potential was highly sensitive to changes in extracellular K + , intracellular Na + , and intracellular ATP levels ( Fig.…”

Effects of Glucose-Induced Insulin Secretion on Ventricular Repolarization in Patients With Congenital Long QT Syndrome

“…The younger aged control group in the present study had low insulin levels within a narrow range compared with the middle-aged volunteers in our previous study, 3 so the different responses to insulin between 2 control groups might caused by dose-dependent effects of insulin on the maximal QT interval and QT dispersion. Insulin has been shown to cause hyperpolarization of the membrane potential through activation of the Na + -K + pump, [24][25][26] which could also produce a high K + gradient across the cell membrane with depletion of K + from the narrow extracellular space. Although the serum K + concentrations were unchanged after glucose load in both groups in the present study, the possibility that an increased K + gradient could affect the repolarization process differently among the 3 regions of the ventricular wall cannot be excluded, and might contribute to the abnormalities observed in LQTS.…”

Dynamics of blood electrolytes in repeated hyper- and/or hypoglycaemic events in patients with type 1 diabetes

“…In fact, hypokalaemia is now a well-established consequence of insulin-induced hypoglycaemia and is caused both by insulin itself and the counter-regulatory hormone adrenaline (epinephrine), secreted in response to hypoglycaemia [6,7]. Experimental work on many different tissues in vitro has shown that insulin has a stimulating effect on the Na + /K + pump [8][9][10]. In vivo, in studies in humans, this stimulatory effect on the Na + /K + pump is active at baseline insulin levels [11], and has been shown to be the cause of insulin-induced decreases in plasma K + after local perfusion of the forearm with insulin [12,13].…”