AXONAL CONTACT REGULATES EXPRESSION OF ALPHA-2 AND BETA-2 ISOFORMS OFNA-ATPASE IN SCHWANN-CELLS - ADHESION MOLECULES AND NERVE REGENERATION(,K+)

Three isoforms of catalytic alpha subunits and two isoforms of beta su bunits of Na+,K+-ATPase were detected in rat sciatic nerves by western blotting. Unlike the enzyme in brain, sciatic nerve Na+,K+-ATPase was highly resistant to ouabain. The ouabain-resistant alpha 1 isoform wa s demonstrated to be the predominant form in rat intact sciatic nerve by quantitative densitometric analysis and is mainly responsible for s ciatic nerve Na+,K+-ATPase activity. After sciatic nerve injury, the a lpha 3 and beta 1 isoforms completely disappeared from the distal segm ent owing to Wallerian degeneration. In contrast, alpha 2 and beta 2 i soform expression and Na+,K+-ATPase activity sensitive to pyrithiamine (a specific inhibitor of the alpha 2 isoform) were markedly increased in Schwann cells in the distal segment of the injured sciatic nerve. These latter levels returned to baseline with nerve regeneration. Our results suggest that alpha 3 and beta 1 isoforms are exclusive for the axon and alpha 2 and beta 2 isoforms are exclusive for the Schwann ce ll, although axonal contact regulates alpha 2 and beta 2 isoform expre ssions, Because the beta 2 isoform of Na+,K+-ATPase is known as an adh esion molecule on glia (AMOG), increased expression of AMOG/beta 2 on Schwann cells in the segment distal to sciatic nerve injury suggests t hat AMOG/beta 2 may act as an adhesion molecule in peripheral nerve re generation.