Characterization of bumetanide-sensitive Na+ and K+ transport in rat skeletal muscle.

Abstract

In isolated rat soleus muscle an average of 23% of the total 22Na influx was found to be suppressible by bumetanide (K0.5 = 0.1 mM) and furosemide (K0.5 = 1 mM), whereas the influx and efflux of 42K were not affected. In extensor digitorum longus muscle, around 25% of the total 22Na influx was suppressible by bumetanide (1 mM). In the presence of ouabain, both diuretics decreased net intracellular accumulation of Na+, but caused no change in K+ content. In extensor digitorum longus (but not in soleus), bumetanide-suppressible 22Na influx was stimulated by increasing extracellular osmolarity with the bumetanide having no effect on 42K influx. Bumetanide-suppressible Na+ influx was almost abolished in Cl(-)-free buffer, but was unaffected by the omission of K+. In rat soleus, the inhibitory effects of bumetanide, amiloride and tetrodotoxin on 22Na influx were found to be additive. The results indicate that a NaCl cotransport system is present in both fast- and slow-twitch skeletal muscles, and may participate in volume regulation. Due to the large pool of muscle cells, activation of NaKCl2 cotransport is likely to entail the hazards of hypokalemia. The advantage of exerting volume control via NaCl cotransport is that this risk can be avoided.