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

Abstract

In the constant flow perfused rat hind limb, norepinephrine (NE) evoked increases in oxygen uptake (VO2) and lactate efflux (LE) were inhibited by the cardiac glycoside ouabain (1 mM), without interrupting the NE-mediated vasoconstriction. The membrane labilizer veratridine, previously shown to increase VO2 and LE, without increasing perfusion pressure, was also shown to be inhibited by the cardiac glycoside ouabain, as well as by the ouabain analogues digitoxin and digoxin. The stimulatory actions of veratridine on VO2 were inhibitable by low doses of the specific sodium channel blocker tetrodotoxin (TTX), while NE effects were unaffected, suggesting that NE may be acting via a TTX-insensitive sodium channel. It is concluded that agents such as NE (a vasoconstrictor) or veratridine (a membrane labilizer), which stimulate VO2 in the perfused 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 Na+ cycling may be a form of facultative thermogenesis attributable to NE that can be stimulated by membrane labilizers such as veratridine in the constant flow perfused rat hind limb.

Hematological and acid-base changes in men during prolonged exercise with and without sodium-lactate infusion

“…The present study can neither confirm nor discount these possibilities. However, we speculate that there is an increased requirement for cellular Na ϩ /K ϩ pumping during LC and that in-creased Na ϩ -K ϩ -ATPase activity may at least partially contribute to the increased V O 2 (41).…”

Absence of adaptive nonshivering thermogenesis in a marsupial, the fat-tailed dunnart (Sminthopsis crassicaudata)

“…It has been hypothesized, that in the absence of BAT, the adrenergic stimulation of all major tissues apart from the brain might be involved (Cannon and Nedergaard 2004), reducing thermogenesis to a purely pharmacological response. An increased metabolism and blood flow due to NA application has been found in muscle tissue of the rat (Mejsnar and Jansky 1971;Tong et al 1999) and NA-induced thermogenesis in marsupials has been attributed to the response of muscle tissue (Holloway and Geiser 2001;Nicol 1978). NST capacity (ml O 2 g -1 h -1 ) for eutherians (black circles) and marsupials (gray circles) described as the difference between _ VO 2NA and BMR: eutherian NST values from Mzilikazi and Lovegrove (2006) and for marsupials the values are summarized in Table 1.…”

Uncoupling of sarcoendoplasmic reticulum calcium ATPase pump activity by sarcolipin as the basis for muscle non-shivering thermogenesis

“…The potential role of SERCA in muscle NST in mammals was initially proposed by the studies of de Meis and co-workers [31][32][33][34][35][36][37]. A few other mechanisms for muscle NST have been proposed including a role for Na + -K + ATPase [38,39], proton leak in the mitochondria [40] and adenine nucleotide translocator (ANT)-mediated mitochondrial heat production [41,42]. However, none of these mechanisms have been conclusively demonstrated and are still open for debate.…”