Interaction between Na+/K+-pump and Na+/Ca2+-exchanger modulates intercellular communication.

• 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(+)/Ca(2+)-exchanger leading to an increase in the intracellular calcium concentration ([Ca(2+)](i)) in discrete areas near the plasma membrane. [Ca(2+)](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 [Ca(2+)](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(+)/Ca(2+)-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 [Ca(2+)](i) at low concentrations 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.

Nyckelord

Aniline Compounds

pharmacology

Animals

Aorta

cytology

metabolism

Calcium

metabolism

Cell Communication

physiology

Cell Membrane

physiology

Cells

Cultured

Drug Interactions

Electric Capacitance

Enzyme Inhibitors

pharmacology

Intracellular Membranes

metabolism

Male

Mesenteric Arteries

cytology

metabolism

Muscle

Smooth

Vascular

physiology

Myocytes

Smooth Muscle

drug effects

physiology

Osmolar Concentration

Ouabain

pharmacology

Phenyl Ethers

pharmacology

Potassium Channel Blockers

pharmacology

Rats

Rats

Wistar

Sodium-Calcium Exchanger

antagonists & inhibitors

physiology

Sodium-Potassium-Exchanging ATPase

antagonists & inhibitors

physiology

Tissue Distribution

Vasoconstriction

drug effects

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