Vladimir Matchkov

Molecular basis for interaction of Na+/K+-ATPase with other transporters in membrane microdomains of vascular smooth muscle cells.

Research output: Contribution to book/anthology/report/proceedingArticle in proceedingsResearchpeer-review

  • Danish Biomembrane Research Centre
  • Department of Physiology and Biophysics

Ouabain, a specific inhibitor of the Na+/K+-pump, has previously been shown to interfere with intercellular communication. We have recently demonstrated a mechanism of this action of ouabain (1). We have showed that gap junctions between vascular smooth muscle cells (SMCs) are regulated through an interaction between the Na+/K+-pump and the Na+/Ca2+-exchanger leading to an increase in the intracellular calcium concentration in discrete areas near the plasma membrane. This regulation suggests a close association of the proteins in microdomains. We have also suggested that this Na+/K+-pump-containing microdomain is functionally linked to KATP channels via the local ion homeostasis and that this interaction can be bidirectional (1;2).

Using PCR, Western blotting and immunohistochemistry we aimed to identify the isoforms of membrane transporters involved in the suggested interaction in SMCs from mesenteric small arteries and in the SMC cell line A7r5. Confocal microscopy and conventional patch clamp were used in functional studies.

The Na+/K+-ATPase subunits in SMCs were found to be α1 and α2. As indicated by loss of mechanical synchronization and synchronization of Ca2+ transients between SMCs and by direct measurements of electrical coupling between SMCs, ouabain effectively uncouples SMCs in micromolar concentrations (1-10 µM). Since rodent α1 Na+/K+-ATPase subunits are ouabain-resistant, we conclude that α2 Na+/K+-ATPase subunits is involved in regulation of the intercellular communications via interaction with the Na+/Ca2+-exchanger in spatially restricted spaces.

Original languageEnglish
Title of host publicationthe Journal of Vascular Research
Number of pages1
Publication year2008
Pages19
Publication statusPublished - 2008
Event9TH INTERNATIONAL SYMPOSIUM ON RESISTANCE ARTERIES (ISRA) - HAMILTON ISLAND, Australia
Duration: 17 Feb 200821 Feb 2008
Conference number: 9

Conference

Conference9TH INTERNATIONAL SYMPOSIUM ON RESISTANCE ARTERIES (ISRA)
Nummer9
LandAustralia
ByHAMILTON ISLAND
Periode17/02/200821/02/2008

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