Matchkov, Vladimir5; Hansen, Anne Kirstine3; Nilsson, Holger4; Aalkjær, Christian5
1 Danish Biomembrane Research Centre, Faculty of Health Sciences, Aarhus University, Aarhus University2 Department of Biomedicine - Forskning og uddannelse, Vest, Department of Biomedicine, Health, Aarhus University3 Institut for Fysiologi og Biofysik, Aarhus Universitet4 Department of Physiology and Biophysics, Faculty of Health Sciences, Aarhus University, Aarhus University5 Department of Biomedicine - Forskning og uddannelse, Vest, Department of Biomedicine, Health, Aarhus University
Ouabain, an inhibitor of the Na+/K+-pump, has previously been shown to disturb intercellular communication. Here we test the hypothesis that the communication between vascular smooth muscle cells (SMCs) is regulated through an interaction between the Na+/K+-pump and the Na+/Ca2+-exchanger in restricted spaces near the plasma membrane. The intracellular Ca2+ concentration ([Ca2+]i) in individual SMCs was imaged simultaneously with isometric force in rat mesenteric small arteries. Paired cultured rat aortic smooth muscle cells (A7r5) were used as a model for electrical coupling of SMC by measuring membrane capacitance (Cm). SMCs were uncoupled (evaluated by inhibition of vasomotion and desynchronization of [Ca2+]i transients in vascular wall, or by reduction of Cm measured in electrically coupled A7r5 cells) when the Na+/K+-pump was inhibited either by a low concentration of ouabain (1-10 µM) or by ATP depletion. Reduction of Na+/K+-pump activity by removal of extracellular K+ also uncoupled cells, but only after inhibition of KATP channels. Inhibition of the Na+/Ca2+-exchange activity by SEA0400 or by lowering the extracellular Na+ concentration also uncoupled the cells. Depletion of [Na+]i and clamping low [Ca2+]i prevented the uncoupling. The experiments suggest that the Na+/K+-pump may affect gap junction conductivity via localized changes in [Ca2+]i through modulation of Na+/Ca2+-exchanger activity.