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 (235·0 ± 51·1 pg/ml) than postsurgery (64·5 ± 25·1 pg/ml) patients. Similarly, Na(+) -K(+) -ATPase activity, relative mRNA expression of α(2) (not α(1) or α(3) ) and β(1) (not β(2) or β(3) ), and protein abundance of α(2) and β(1) subunits were greater in pre- than postsurgery samples (128·7 ± 12·3 vs 79·4 ± 13·3 nmol·mg/protein/h, 2·45 ± 0·31 vs 1·04 ± 0·17, 1·92 ± 0·22 vs1·02 ± 0·14, 2·17 ± 0·33 vs 0·98 ± 0·09 and 1·70 ± 0·17 vs 0·90 ± 0·17, respectively, all P<0·05). The activity and mRNA expression of the α(2) and β(1) subunits correlated well with plasma aldosterone levels (r = 0·71, r = 0·75 and r = 0·78, respectively, all P < 0·01).
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 α(2) and β(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.
© 2011 Blackwell Publishing Ltd.