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

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Abstract
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). 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. 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. 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. RT–PCR, Western blotting and immunohistochemical techniques collectively showed the presence of α1‐, α2‐ and α3‐subunits of Na+/K+‐ATPase in the myocytes. 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. We conclude that under basal conditions, Na+/K+‐ATPases containing α2‐ and/or α3‐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. British Journal of Pharmacology (2002) 136, 918–926. doi:10.1038/sj.bjp.0704787

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