Intracellular pH modulates spontaneous and epileptiform bioelectric activity of hippocampal CA3-neurones

A growing body of evidence hints at intracellular free protons to be involv ed in the modulation of electric activity of cortical neurones. In this stu dy we demonstrate that application of the weak acid propionate (2.5-20 mM) transiently lowers intracellular PH (pH(i)) of BCECF-AM loaded CA3-neurones in hippocampal slices. The predictability of this acidification prompted u s to use propionate as a tool to investigate effects of pH(i) on spontaneou s bioelectric activity (SBA) and epileptiform activity (EA, induced by bicu culline, caffeine or low magnesium) of CA3 neurones: SEA and EA were transi ently suppressed by 2-20 mM propionate - coinciding with the transient neur onal acidification. As activation of Na+ /H+-exchangers (NHE) is involved i n the recovery from neuronal acidosis and NHE-inhibition alone is known to increase the activity of intracellular free protons of hippocampal neurones , we tested the effect of the NHE-blockers amiloride (0.5-1 mM) or HOE642 ( 200 mu M) on SEA and EA of CA3-neurones. Long-term application of NHE-inhib itors alone continuously suppressed SEA and EA, which recovered during addi tional exposure to the weak base trimethylamine (5-10 mM). Simultaneous adm inistration of propionate and NHE-blockers intensified the inhibition of ne uronal activity. Together, these results indicate that intracellular acidif ication inhibits bioelectric activity of hippocampal CA3-neurones. This sup ports the hypothesis that pH(i) contributes to the control of cortical exci tability. (C) 2000 Elsevier Science B.V. All rights reserved.