Aldosterone increases Na plus -K plus -ATPase activity in skeletal muscle of patients with Conn's syndrome

P>Objective In Conn's syndrome, hypokalaemia normally results from renal potassium loss because of the effect of excess aldosterone on Na+-K+-ATPase in principal cells. Little is known about the effect of aldosterone on cellular potassium redistribution in skeletal muscle. Our study determined the effect of aldosterone on muscle Na+-K+-ATPase. Design Muscle biopsies were taken from six patients immediately before and 1 month after adrenalectomy. Ten age-matched subjects with normal levels of circulating aldosterone served as controls. Results Average plasma aldosterone was significantly higher in presurgery (235 center dot 0 +/- 51 center dot 1 pg/ml) than postsurgery (64 center dot 5 +/- 25 center dot 1 pg/ml) patients. Similarly, Na+-K+-ATPase activity, relative mRNA expression of alpha(2) (not alpha(1) or alpha(3)) and beta(1) (not beta(2) or beta(3)), and protein abundance of alpha(2) and beta(1) subunits were greater in pre- than postsurgery samples (128 center dot 7 +/- 12 center dot 3 vs 79 center dot 4 +/- 13 center dot 3 nmol center dot mg/protein/h, 2 center dot 45 +/- 0 center dot 31 vs 1 center dot 04 +/- 0 center dot 17, 1 center dot 92 +/- 0 center dot 22 vs1 center dot 02 +/- 0 center dot 14, 2 center dot 17 +/- 0 center dot 33 vs 0 center dot 98 +/- 0 center dot 09 and 1 center dot 70 +/- 0 center dot 17 vs 0 center dot 90 +/- 0 center dot 17, respectively, all P < 0 center dot 05). The activity and mRNA expression of the alpha(2) and beta(1) subunits correlated well with plasma aldosterone levels (r = 0 center dot 71, r = 0 center dot 75 and r = 0 center dot 78, respectively, all P < 0 center dot 01). Conclusions Our study provides the first evidence in human skeletal muscle that increased plasma aldosterone leads to increased Na+-K+-ATPase activity via increases in alpha(2) and beta(1) subunit mRNAs and their protein expressions. The increased activity may contribute in part to the induction of hypokalaemia in patients with Conn's syndrome.