Tj. Hawke et al., Ouabain stimulates unidirectional and net potassium efflux in resting mammalian skeletal muscle, CAN J PHYSL, 79(11), 2001, pp. 932-941
The present study compared ouabain-sensitive unidirectional K+ flux into (J
inK) and out of (JoutK) perfused rat hindlimb skeletal muscle in situ and m
ouse flexor digitorum brevis (FDB) in vitro. In situ, 5 mM ouabain inhibite
d 54 +/- 4% of the total JinK in 28 +/- 1 min, and increased the net and un
idirectional efflux of K+ within 4 min. In contrast, 1.8 mM ouabain inhibit
ed 40 +/- 8% of the total JinK in 38 +/- 2 min, but did not significantly a
ffect JoutK. In vitro, 1.8 and 0.2 mM ouabain decreased JinK to a greater e
xtent (83 +/- 5%) than in situ, but did not significantly affect K-42 loss
rate compared with controls. The increase in unidirectional K+ efflux (Jout
K) with 5 mM ouabain in situ was attributed to increased K+ efflux through
cation channels, since addition of barium (1 mM) to ouabain-perfused muscle
s returned JoutK to baseline values within 12 min. Perfusion with 5 mM ouab
ain plus 2 mM tetracaine for 30 min decreased JinK 46 +/- 9% (0.30 +/- 0.03
to 0.16 +/- 0.02 mu mol.min(-1).g(-1)), however tetracaine was unable to a
bolish the ouabain-induced increase in unidirectional K+ efflux. In both ra
t hindlimb and mouse FDB, tetracaine had no effect on JoutK. Perfusion of h
indlimb muscle with 0.1 mM tetrodotoxin (TTX, a Na+ channel blocker) decrea
sed JinK by 15 +/- 1%, but had no effect on JoutK; subsequent addition of o
uabain (5 mM) decreased JinK a further 32 +/- 2%. The ouabain-induced incre
ase in unidirectional K+ efflux did not occur when TTX was perfused prior t
o and during perfusion with 5 mM ouabain. We conclude that 5 mM ouabain inc
reases the unidirectional efflux of K+ from skeletal muscle through a bariu
m and TTX-sensitive pathway, suggestive of voltage sensitive Na+ channels,
in addition to inhibiting Na+/K+-ATPase activity.