Effects of Cations on Brown Adipose Tissue in Relation to Possible Metabolic Consequences of Membrane Depolarisation

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Abstract
Norepinephrine‐stimulated respiration of isolated hamster brown fat cells is only slightly dependent upon the extracellular concentration of Mg2+ and Ca2+, but very dependent upon K+ and Na+. The inhibition of respiration in the absence of K+ is caused by diminished norepinephrine‐stimulated fatty acid release. However, in the absence of Na+. norepinephrine‐stimulated fatty acid release proceeds virtually unaffected. Na+‐stimulated Ca2+ release from isolated brown fat mitochondria is higher in preparations from cold‐adapted rats than from control rats. The extramitochondrial (‘cytosolic’) Ca2+, level is regulated by Na+ in the range 5–25 mM. K+ in the range 0–20 mM decreases mitochondrial Ca2+ uptake and thus promotes the effect of Na+ on the extramitochondrial steady‐state level of Ca2+. Energy dissipating Na+‐induced Ca2+‐cycling is only of minor thermogenic importance. Mitochondrial glycerol‐3‐phosphate dehydrogenase is indirectly regulated by Na+ through an increase in extramitochondrial Ca2+. Lack of Na+ in the incubation medium for brown fat cells abolishes the inhibitory effect of norepinephrine addition on triacylglycerol synthesis. It is suggested that the norepinephrine‐induced plasma membrane depolarisation in brown fat cells leads, through the increased Na+ entry, to elevated cytosolic levels of Na+, and that this Na+ has metabolic consequences: it increases the cytosolic Ca+ level, and this Ca+ may regulate enzyme systems, including glycerol‐3‐phosphate dehydrogenase. Lowered levels of glycerol 3‐phosphate within brown fat cells may reduce the rate of fatty acid esterification and, in consequence, acyl‐CoA may be directed towards oxidation.