K +-induced hyperpolarization in rat mesenteric artery: Identification, localization and role of Na +/K +-ATPases

A. H. Weston, G. R. Richards, M. P. Burnham, M. Félétou, P. M. Vanhoutte, G. Edwards

    Research output: Contribution to journalArticlepeer-review


    1. Mechanisms underlying K +-induced hyperpolarizations in the presence and absence of phenylephrine were investigated in endothelium-denuded rat mesenteric arteries (for all mean values, n = 4). 2. Myocyte resting membrane potential (m.p.) was -58.8±0.8 mV. Application of 5 mM KCl produced similar hyperpolarizations in the absence (17.6±0.7 mV) or presence (15.8±1.0 mV) of 500 nM ouabain. In the presence of ouabain +30 μM barium, hyperpolarization to 5 mM KCl was essentially abolished. 3. In the presence of 10 μM phenylephrine (m.p. -33.7±3 mV), repolarization to 5 mM KCl did not occur in the presence or absence of 4-aminopyridine but was restored (-26.9±1.8 mV) on addition of iberiotoxin (100 nM). Under these conditions the K +-induced repolarization was insensitive to barium (30 μM) but abolished by 500 nm ouabain alone. 4. In the presence of phenylephrine + iberiotoxin the hyperpolarization to 5 mM K + was inhibited in the additional presence of 300 nM levcromakalim, an action which was reversed by 10 μM glibenclamide. 5. RT-PCR, Western blotting and immunohistochemical techniques collectively showed the presence of α 1-, α 2- and α 3-subunits of Na +/K +-ATPase in the myocytes. 6. In K +-free solution, re-introduction of K + (to 4.6 mM) hyperpolarized myocytes by 20.9±0.5 mV, an effect unchanged by 500 nM ouabain but abolished by 500 μM ouabain. 7. We conclude that under basal conditions, Na +/K +-ATPases containing α 2- and/or α 3-subunits are partially responsible for the observed K +-induced effects. The opening of myocyte K + channels (by levcromakalim or phenylephrine) creates a 'K + cloud' around the cells which fully activates Na +/K +-ATPase and thereby abolishes further responses to [K +] o elevation.
    Original languageEnglish
    Pages (from-to)918-926
    Number of pages8
    JournalBritish Journal of Pharmacology
    Issue number6
    Publication statusPublished - 2002


    • 4-aminopyridine
    • EDHF
    • Hyperpolarization
    • Iberiotoxin
    • Immuno-histochemistry
    • Na +/K +-ATPase isoforms
    • Ouabain
    • Phenylephrine
    • Potassium


    Dive into the research topics of 'K +-induced hyperpolarization in rat mesenteric artery: Identification, localization and role of Na +/K +-ATPases'. Together they form a unique fingerprint.

    Cite this