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.