Acy. Tong et al., Na+ channel and Na+-K+ ATPase involvement in norepinephrine- and veratridine-stimulated metabolism in perfused rat hind limb, CAN J PHYSL, 77(5), 1999, pp. 350-357
In the constant flow perfused rat hind limb, norepinephrine (NE) evoked inc
reases in oxygen uptake ((V)over dot O-2) and lactate afflux (LE) were inhi
bited by the cardiac glycoside ouabain (1 mM), without interrupting the NE-
mediated vasoconstriction. The membrane labilizer veratridine, previously s
hown to increase (V)over dot O-2 and LE, without increasing perfusion press
ure, was also shown to be inhibited by the cardiac glycoside ouabain, as we
ll as by the ouabain analogues digitoxin and digoxin. The stimulatory actio
ns of veratridine on (V)over dot O-2 were inhibitable by low doses of the s
pecific sodium channel blocker tetrodotoxin (TTX), while NE effects were un
affected, suggesting that NE may be acting via a TTX-insensitive sodium cha
nnel. It is concluded that agents such as NE (a vasoconstrictor) or veratri
dine (a membrane labilizer). which stimulate (V)over dot O-2 in the perfuse
d rat hind limb, do so by increasing Na+ influx. The observed increases in
oxygen consumption and LE are due to Na+-K+ ATPase activity to pump Na+ out
of the cell at the expense of ATP turnover. Energy dissipation due to Nacycling may be a form of facultative thermogenesis attributable to NE that
can be stimulated by membrane labilizers such as veratridine in the constan
t flow perfused rat hind limb.