Na+ channel and Na+-K+ ATPase involvement in norepinephrine- and veratridine-stimulated metabolism in perfused rat hind limb

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.