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Department of Cardiology, 1 Royal North Shore Hospital, and 2 University of Sydney, Sydney, New South Wales 2065, Australia
To examine the effect of aldosterone on sarcolemmal
Na+ transport, we measured
ouabain-sensitive electrogenic
Na+-K+
pump current
(Ip) in
voltage-clamped ventricular myocytes and intracellular
Na+ activity
(aiNa) in right ventricular
papillary muscles. Aldosterone (10 nM) induced an increase in both
Ip and the rate
of rise of aiNa during
Na+-K+
pump blockade with the fast-acting cardiac steroid dihydroouabain. The
aldosterone-induced increase in
Ip and rate of
rise of aiNa was eliminated by
bumetanide, suggesting that aldosterone activates Na+ influx through the
Na+-K+-2Cl
cotransporter. To obtain independent support for this, the
Na+,
K+, and
Cl
concentrations in the
superfusate and solution of pipettes used to voltage clamp myocytes
were set at levels designed to abolish the inward electrochemical
driving force for the
Na+-K+-2Cl
cotransporter. This eliminated the aldosterone-induced increase in
Ip. We conclude
that in vitro exposure of cardiac myocytes to aldosterone activates the
Na+-K+-2Cl
cotransporter to enhance Na+
influx and stimulate the
Na+-K+
pump.
ion transport; intracellular sodium; sodium-potassium-two chloride cotransport; mineralocorticoid receptor; cell membrane
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