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Cardiovascular Research 1997 33(3):548-560; doi:10.1016/S0008-6363(97)00009-6
© 1997 by European Society of Cardiology
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Copyright © 1997, European Society of Cardiology

Effects of elevating [Na]i on membrane currents of canine ventricular myocytes: role of intracellular Ca ions

Nina Chandramani Saxena1, Jing-Song Fan and Gea-Ny Tseng*

Department of Pharmacology, Columbia University, 630 West 168th Street, New York, NY 10032, USA

Objectives: Our first objective was to study how elevating [Na]i can modify the background membrane conductance in canine ventricular myocytes (CVM). In particular, we wanted to find evidence for a Nai-activated K current (IK,Na) in these cells. The second objective was to compare the effects of elevating [Na]i on membrane currents without and with intracellular Ca buffering. Methods: Whole-cell currents were recorded and [Na]i was elevated either by using a pipette perfusion device that allowed [Na] in the pipette solution to be varied (from 0 to 50 mM), or by 50 µM ouabain. Results: Although an outward current attributable to IK,Na was confirmed in guinea-pig ventricular myocytes (GPVM) under our recording conditions, no such current was seen in 29 CVM examined. With Cai buffering, the main effect of elevating [Na]i on CVM was an increase in inward current around and negative to the resting membrane potential. Based on the dependence of this Nai-induced inward current on K ions and its pharmacological properties, especially the effects of low concentrations of external Ba ions (≤5 µM) at strongly hyperpolarized voltages, we hypothesize that this current was carried by extracellular K ions through the inward rectifier (IKl) channels that had been modified by the high level of [Na]i. With Cai buffering, elevating [Na]i by ouabain had few or no effects on the L-type Ca channel current (ICa) or the slow delayed rectifier current (IKS). Without Cai buffering, ouabain induced a rapid reduction of both currents along with an increase in a time-independent outward current at voltages positive to –60 mV. Conclusion: Our data suggest that there are species variations in K channel expression and/or K channel modulation by intracellular Na ions. Furthermore, intracellular Ca ions play a crucial role in mediating the effects of Nai loading on membrane currents in canine ventricular myocytes.

KEYWORDS Dog, ventricular myocytes; Calcium, intracellular concentration; Sodium, intracellular concentration; Potassium channel, inward rectifier; Potassium channel, Na-activated; Potassium channel, slow delayed rectifier; Calcium channel, L-type


1 Present address: Department of Physiology, Emory University School of Medicine, Atlanta, GA 30322, USA.

* Corresponding author. Tel. +1 212 305-4166; Fax +1 212305-4048. gt10{at}columbia.edu


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