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.
Matchkov
Vladimir V
VV
Water and Salt Research Center, Institute of Physiology and Biophysics, University of Aarhus, Denmark. vvm@fi.au.dk
Gustafsson
Helena
H
Rahman
Awahan
A
Briggs Boedtkjer
Donna M
DM
Gorintin
Sarah
S
Hansen
Anne Kirstine
AK
Bouzinova
Elena V
EV
Praetorius
Helle A
HA
Aalkjaer
Christian
C
Nilsson
Holger
H
D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D004347:Drug Interactions; D025802:Electric Capacitance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000166:cytology / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D009994:Osmolar Concentration; D010042:Ouabain / Q000494:pharmacology; D010647:Phenyl Ethers / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000502:physiology*; D014018:Tissue Distribution; D014661:Vasoconstriction / Q000187:drug effects
D000814:Aniline Compounds; D004791:Enzyme Inhibitors; D010647:Phenyl Ethers; D026902:Potassium Channel Blockers; C430918:SEA 0400; D019831:Sodium-Calcium Exchanger; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium