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(Circulation Research. 2007;100:1026.)
© 2007 American Heart Association, Inc.

Cellular Biology

Interaction Between Na⁺/K⁺-Pump and Na⁺/Ca²⁺-Exchanger Modulates Intercellular Communication

Vladimir V. Matchkov, Helena Gustafsson, Awahan Rahman, Donna M. Briggs Boedtkjer, Sarah Gorintin, Anne Kirstine Hansen, Elena V. Bouzinova, Helle A. Praetorius, Christian Aalkjaer, Holger Nilsson

From the the Water and Salt Research Center, Institute of Physiology and Biophysics (V.V.M., A.R., D.M.B.B., S.G., A.K.H., E.V.B., H.A.P., C.A., H.N.), University of Aarhus, Denmark; Department of Physiology (H.G.), University of Göteborg, Sweden; and the Laboratoire de Biologie Moléculaire et Cellulaire du Développement (S.G.), Université Pierre et Marie Curie, Paris, France.

Correspondence to V.V. Matchkov, Institute of Physiology and Biophysics, University of Aarhus, Ole Worms Alle 160, 8000 Aarhus C, Denmark. E-mail vvm{at}fi.au.dk

Ouabain, a specific inhibitor of the Na⁺/K⁺-pump, has previously been shown to interfere with intercellular communication. Here we test the hypothesis that the communication between vascular smooth muscle cells is regulated through an interaction between the Na⁺/K⁺-pump and the Na⁺/Ca²⁺-exchanger leading to an increase in the intracellular calcium concentration ([Ca²⁺]_i) in discrete areas near the plasma membrane.

[Ca²⁺]_i in smooth muscle cells was imaged in cultured rat aortic smooth muscle cell pairs (A7r5) and in rat mesenteric small artery segments simultaneously with force. In A7r5 coupling between cells was estimated by measuring membrane capacitance.

Smooth muscle cells were uncoupled when the Na⁺/K⁺-pump was inhibited either by a low concentration of ouabain, which also caused a localized increase of [Ca²⁺]_i near the membrane, or by ATP depletion. Reduction of Na⁺/K⁺-pump activity by removal of extracellular potassium ([K⁺]_o) also uncoupled cells, but only after inhibition of K_ATP channels. Inhibition of the Na⁺/Ca²⁺-exchange activity by SEA0400 or by a reduction of the equilibrium potential (making it more negative) also uncoupled the cells. Depletion of intracellular Na⁺ and clamping of [Ca²⁺]_i at low concentrations 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.

Key Words: Na⁺/K⁺-pump • Na⁺/Ca²⁺-exchanger • intercellular communication • [Ca²⁺]_i signaling • ATP-sensitive K⁺ channels

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