THE AMILORIDE-SENSITIVE NA+ H+ EXCHANGE ANTIPORTER AND CONTROL OF INTRACELLULAR PH IN HIPPOCAMPAL BRAIN-SLICES/

The intracellular pH, 7.54 +/- 0.03 (mean +/- S.D., n = 15), determine d with the Neutral red method, of the hippocampal brain slice preparat ion under baseline incubation conditions is considerably more alkaline than the bath buffer pH. Neutralization by amiloride suggests that th e alkalinity was due to Na+/H+ exchange antiporter activation. To char acterize the brain Na+/H+ exchange antiporter we compared the inhibito ry effects of MIA, amiloride and other 5-N substituted analogues on pr oton extrusion after acid loading by transient exposure to ammonium ch loride in the isolated hippocampal brain slice preparation. The potenc ies of amiloride compounds on the initial recovery rate of intracellul ar pH after acid-loading were DMA > MIA > HMA = MHA greater than or eq ual to IPA-HCI > IPA > MNPA = Amil > Benzamil. The greater potency of the 5-N substituted analogs of amiloride over amiloride and benzamil s trongly suggest that Na+/H+ exchange antiporter is the mechanism respo nsible for alkalinization in the isolated hippocampal brain slice in v itro.