Tj. Hawke et al., K+ transport in resting rat hind-limb skeletal muscle in response to paraxanthine, a caffeine metabolite, CAN J PHYSL, 77(11), 1999, pp. 835-843
This study tested the hypothesis that paraxanthine, a caffeine metabolite,
stimulates skeletal muscle potassium (K+) transport by an increase in Na+-K
+ ATPase activity. The unidirectional transport of K+ into muscle (J(in)K)
was studied using a perfused rat hind limb technique. Using 12 hind limbs,
we examined the response to 20 min of paraxanthine perfusion (0.1 mM), foll
owed by 20 min perfusion with 0.1 mM paraxanthine and 5 mM ouabain (n = 5)
to irreversibly inhibit Na+-K+ ATPase activity. Paraxanthine stimulated J(i
n)K by 23 +/- 5% within 20 min. Ouabain abolished the paraxanthine-induced
stimulation of J(in)K, suggesting the increase in K+ uptake was due to acti
vation of the Na+-K+ ATPase. To confirm the role of the Na+-K+ ATPase, 14 h
ind limbs were perfused for 20 min with 5 mM ouabain prior to 20 min perfus
ion with 0.1 mM paraxanthine and 5 mM ouabain (n = 6). Ouabain alone result
ed in a 41 +/- 7% decrease in J(in)K within 15 min. Inhibition of ouabain-s
ensitive J(in)K prevented the paraxanthine-induced increase in J(in)K. Hind
limbs (n = 3) were also perfused with 0.1 mM paraxanthine for 60 min to ex
amine the response to longer duration paraxanthine perfusion. The paraxanth
ine-induced increase in J(in)K continued for the entire 60 min. In another
series, hind limbs were perfused with 0.01 (n = 9), 0.1 (n = 9), or 0.5 (n
= 6) mM paraxanthine for 15 min. There was no concentration-dependent relat
ionship between J(in)K and paraxanthine concentration, and 0.01, 0.1, and 0
.5 mM paraxanthine increased J(in)K similarly (25 +/- 5, 22 +/- 4, and 27 /- 6%, respectively). The effect of paraxanthine on J(in)K could not be rev
ersed by subsequent perfusion with paraxanthine-free perfusate. Caffeine (0
.05-1.0 mM) had no effect on K+ transport. It is concluded that paraxanthin
e increases J(in)K in resting skeletal muscle by stimulating ouabain-sensit
ive Na+-K+ ATPase activity.