Multiple forms of the Na,K-ATPase: their genes and tissue specific expression.

The use of genetic tools has been invaluable for examining the potential number of alpha and beta subunits of the Na,K-ATPase. To date at least five genes corresponding to the alpha subunit have been described. Two of these encode the alpha and alpha+ isoforms while the third encodes the novel alpha III subunit. The products of the other two genes have not yet been described; these genes may be pseudogenes or may encode new alpha isoforms or related transport ATPases. The determination of the tissue distribution of the various isoforms of the alpha subunit using Northern blot and slot blot analyses has yielded several interesting findings. Each tissue differs in the abundance and combination of isoforms. While alpha is the major isoform mRNA in kidney, alpha+ mRNA predominates in skeletal muscle. All three alpha subunit mRNAs are present in brain in roughly equal amounts. The newly discovered alpha III isoform mRNA is found not only in brain but in low amounts in stomach and lung. It is possible that individual cell types may contain a defined combination of isoforms which allow the Na,K-ATPase to fulfill its specific physiological role in those cells. It will be interesting to compare the functional properties, i.e., affinity for Na+ and K+, turnover number, response to external changes in environment and response to effector molecules for the enzymes containing each of the alpha subunit isoforms.