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Ouabain stimulates unidirectional and net potassium efflux in resting mammalian skeletal muscle

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Abstract:

The present study compared ouabain-sensitive unidirectional K+ flux into (JinK) and out of (JoutK) perfused rat hindlimb skeletal muscle in situ and mouse flexor digitorum brevis (FDB) in vitro. In situ, 5 mM ouabain inhibited 54 +- 4% of the total JinK in 28 +- 1 min, and increased the net and unidirectional efflux of K+ within 4 min. In contrast, 1.8 mM ouabain inhibited 40 +- 8% of the total JinK in 38 +- 2 min, but did not significantly affect JoutK. In vitro, 1.8 and 0.2 mM ouabain decreased JinK to a greater extent (83 +- 5%) than in situ, but did not significantly affect 42K loss rate compared with controls. The increase in unidirectional K+ efflux (JoutK) with 5 mM ouabain in situ was attributed to increased K+ efflux through cation channels, since addition of barium (1 mM) to ouabain-perfused muscles returned JoutK to baseline values within 12 min. Perfusion with 5 mM ouabain plus 2 mM tetracaine for 30 min decreased JinK 46 +- 9% (0.30 +- 0.03 to 0.16 +- 0.02 molmin-1g-1), however tetracaine was unable to abolish the ouabain-induced increase in unidirectional K+ efflux. In both rat hindlimb and mouse FDB, tetracaine had no effect on JoutK. Perfusion of hindlimb muscle with 0.1 mM tetrodotoxin (TTX, a Na+ channel blocker) decreased JinK by 15 +- 1%, but had no effect on JoutK; subsequent addition of ouabain (5 mM) decreased JinK a further 32 +- 2%. The ouabain-induced increase in unidirectional K+ efflux did not occur when TTX was perfused prior to and during perfusion with 5 mM ouabain. We conclude that 5 mM ouabain increases the unidirectional efflux of K+ from skeletal muscle through a barium and TTX-sensitive pathway, suggestive of voltage sensitive Na+ channels, in addition to inhibiting Na+/K+-ATPase activity.Key words: cardiac glycoside, Na,K pump, K+ channels, Na+ channels, perfused rat hindlimb, flexor digitorum brevis, TTX, barium, tetracaine.

Keywords: K pump; K+ channels; Na; Na+ channels; Na+-K+; TTX; barium; baryum; canaux K+; canaux Na+; cardiac glycoside; de rat; flexor digitorum brevis; glucoside cardiotonique; membre postérieur perfusé; muscle court fléchisseur plantaire; perfused rat hindlimb; pompe à; tetracaine; tétracaïne

Document Type: Research Article

Publication date: November 1, 2001

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  • Published since 1929, this monthly journal reports current research in all aspects of physiology, nutrition, pharmacology, and toxicology, contributed by recognized experts and scientists. It publishes symposium reviews and award lectures and occasionally dedicates entire issues or portions of issues to subjects of special interest to its international readership.
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