The alpha(1)- and alpha(2)-isoforms of Na-K-ATPase play different roles inskeletal muscle contractility

The Na-K-ATPase, which maintains the Na+ and K+ gradients across the plasma membrane, can play a major role in modulation of skeletal muscle contracti lity. Although both alpha (1)- and alpha (2)-isoforms of the Na-K-ATPase ar e expressed in skeletal muscle, the physiological significance of these iso forms in contractility is not known. Evaluation of the contractile paramete rs of mouse extensor digitorum longus (EDL) was carried out using gene-targ eted mice lacking one copy of either the alpha (1)- or alpha (2)-isoform ge ne of the Na-K-ATPase. The EDL muscles from heterozygous mice contain appro ximately one-half of the alpha (1)- or alpha (2)-isoform, respectively, whi ch permits differentiation of the functional roles of these isoforms. EDL f rom the alpha (+/-)(1) mouse shows lower force compared with wild type, whe reas that from the alpha (+/-)(2) mouse shows greater force. The different functional roles of these two isoforms are further demonstrated because inh ibition of the alpha (2)-isoform with ouabain increases contractility of al pha (+/-)(1) EDL. These results demonstrate that the Na-K-ATPase a,and alph a (2)-isoforms may play different roles in skeletal muscle contraction.