Na + /K + ‐pump modulates intercellular communication via interaction with other membrane transporters in vascular smooth muscle cells.

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 + /Ca 2+ ‐exchanger in restricted spaces near the plasma membrane. The intracellular Ca 2+ concentration ([Ca 2+ ] 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 [Ca 2+ ] 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 K ATP channels. Inhibition of the Na + /Ca 2+ ‐exchange activity by SEA0400 or by lowering the extracellular Na + concentration also uncoupled the cells. Depletion of [Na + ] i and clamping low [Ca 2+ ] i prevented the uncoupling. The experiments suggest that the Na + /K + ‐pump may affect gap junction conductivity via localized changes in [Ca 2+ ] i through modulation of Na + /Ca 2+ ‐exchanger activity.