CONTROL OF THE NA-ATPASE UNDER NORMAL AND PATHOLOGICAL CONDITIONS(,K+)

The Na+,K+-ATPase is an important enzyme in determining the ionic mili eu of the cerebromicrovasculature and neurons. The effect of hypertens ion or aging on this enzyme, as well as its susceptibility to regulati on by fatty acids or aluminum, is the focus of this study. A significa nt increase (34%) in the apparent affinity constant (K(D)) but no chan ge in the maximum binding capacity (B(max)) for [H-3]ouabain binding t o the cerebromicrovascular Na+,K+-ATPase occurs after induction of acu te hypertension. In addition, long chain unsaturated fatty acids stimu late the binding of [H-3]ouabain to the enzyme in microvessels from no rmotensive and hypertensive rats. The synaptosomal Na+,K+-ATPase is se nsitive to aluminum. AlCl3 (1-100 muM) inhibits the K+-dependent-p-nit rophenylphosphatase (K+-NPPase) activity of the Na+,K+-ATPase in a dos e-dependent manner. AlC13 (100 muM) decreases the V(max) by 14% but do es not alter the K(M), suggestive of noncompetitive inhibition. The en zyme from aged brain displays a greater V(max), but shows the same sus ceptibility to AlC13 as the enzyme from younger brain. In summary, dis ruption of the Na+,K+-ATPase may underlie, at least in part, abnormali ties of nerve and vascular cell function in disorders where elevated c oncentrations of fatty acids or metal ions are involved.