Role of kinases and G-proteins in the hyposmotic stimulation of cardiac IKs

Sergey Missan, Paul Linsdell, Terence F. McDonald

Résultat de recherche: Articleexamen par les pairs

6 Citations (Scopus)

Résumé

Exposure of cardiac myocytes to hyposmotic solution stimulates slowly-activating delayed-rectifying K+ current (IKs) via unknown mechanisms. In the present study, IKs was measured in guinea-pig ventricular myocytes that were pretreated with modulators of cell signaling processes, and then exposed to hyposmotic solution. Pretreatment with compounds that (i) inhibit serine/threonine kinase activity (10-100 μM H89; 200 μM H8; 50 μM H7; 1 μM bisindolylmaleimide I; 10 μM LY294002; 50 μM PD98059), (ii) stimulate serine/threonine kinase activity (1-5 μM forskolin; 0.1 μM phorbol-12-myristate-13-acetate; 10 μM acetylcholine; 0.1 μM angiotensin II; 20 μM ATP), (iii) suppress G-protein activation (10 mM GDPβS), or (iv) disrupt the cytoskeleton (10 μM cytochalasin D), had little effect on the stimulation of IKs by hyposmotic solution. In marked contrast, pretreatment with tyrosine kinase inhibitor tyrphostin A25 (20 μM) strongly attenuated both the hyposmotic stimulation of IKs in myocytes and the hyposmotic stimulation of current in BHK cells co-expressing Ks channel subunits KCNQ1 and KCNE1. Since attenuation of hyposmotic stimulation was not observed in myocytes and cells pretreated with inactive tyrphostin A1, we conclude that TK has an important role in the response of cardiac Ks channels to hyposmotic solution.

Langue d'origineEnglish
Pages (de-à)1641-1652
Nombre de pages12
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1758
Numéro de publication10
DOI
Statut de publicationPublished - oct. 2006

Note bibliographique

Funding Information:
We thank Ms. Gina Dickie for excellent technical assistance. This study was supported by the Canadian Institutes of Health Research and the Heart and Stroke Foundation of New Brunswick.

ASJC Scopus Subject Areas

  • Biophysics
  • Biochemistry
  • Cell Biology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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