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Weston AH, Richards GR, Burnham MP, Feletou M, Vanhoutte PM, Edwards G: K+-induced hyperpolarization in rat mesenteric artery: identification, localization and role of Na+/K+-ATPases. Br J Pharmacol. 2002 Jul;136(6):918-26.
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 microM barium, hyperpolarization to 5 mM KCl was essentially abolished. 3. In the presence of 10 microM 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 microM) 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 microM glibenclamide. 5. RT-PCR, Western blotting and immunohistochemical techniques collectively showed the presence of alpha (1)-, alpha (2)- and alpha (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 microM ouabain. 7. We conclude that under basal conditions, Na (+)/K (+)-ATPases containing alpha (2)- and/or alpha (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. |
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