?-Adrenergic modulation of the Na+?K+ pump in frog skeletal muscles

Abstract

Adrenaline markedly increased the ouabain-sensitive 22Na+-efflux by stimulating the Na+-K+ pump in frog skeletal muscle. The facilitatory effects of adrenaline had the following properties. The effects of adrenaline on the ouabain-sensitive Na+-efflux were observed at concentrations greater than 0.1 microM and the magnitude increased with concentration up to 10 microM. At a concentration of 30 microM, adrenaline markedly augmented the ouabain-sensitive Na+-efflux, but other biogenic amines were less effective (noradrenaline and dopamine) or ineffective (histamine and serotonin). The increase of Na+-efflux induced by 1 microM adrenaline was blocked by 3 microM propranolol, but not by 3 microM phenoxybenzamine. The properties of the facilitatory action of adrenaline on the ouabain-sensitive Na+-efflux suggest that beta-adrenoceptors have an important role in modulating the Na+-K+ pump activity in the skeletal muscle membrane. The protein complex localized in excitable membranes, namely the Na+-K+ ATPase-beta-adrenoceptor complex, may be the functional unit which operates the membrane machinery driving the Na+-K+ pump.

Na,K-ATPase regulation in skeletal muscle

“…Among endogenous catecholamines, epinephrine is the most potent stimulator of NKA in skeletal muscle (65,167). The threshold for epinephrine-stimulated activation of NKA in isolated skeletal muscle is ϳ6 nM, whereas half-maximal stimulation is achieved by 13 nM (65).…”

Mechanisms of sodium pump regulation

“…In particular, adrenergic agents such as epinephrine and norepinephrine have been found to specifically stimulate sodium pump activity (for examples, see Refs. 1,12,20,69,94,150,162,175,314,342). Like dopamine, their effects on activity are probably tissue specific.…”

“…Thus catecholamine-dependent increases in cAMP levels, and, therefore, stimulation of PKA, have been shown to activate Na ϩ -K ϩ -ATPase of brown adipose tissue (162), ventricular myocytes (132), kidney cortex (139), smooth muscle of the stomach (234) and arteries (344), skeletal muscle (206), and macrophages (98), whereas PKC-mediated pathways appear to be responsible for sodium pump stimulation in hepatocytes (217), ventricular myocytes (342), and skeletal muscle (206). Regulation can be mediated through ␣-adrenergic receptors (12,342), ␤-adrenergic receptors (1,175), or both (162,314). Generally, ␤-adrenergic stimulation is associated with activation of PKA pathways, whereas ␣-adrenergic agents stimulate PKC-dependent effects.…”