K+-evoked [3H]-norepinephrine release in human brain slices from epileptic and non-epileptic patients is differentially modulated by gabapentin and pinacidil

The modulation of K+-evoked [3H]-norepinephrine ([3H]-NE) release by gabapentin (GBP) and pinacidil (PIN), a known KATP agonist, was examined in human brain slices. We compared the pharmacological effects on NE-release in human epileptic neocortex and epileptic hippocampus to non-epileptic neocortex. GBP (100 μM) decreased [3H]-NE release by 22% in non-epileptic neocortical slices, whereas this inhibition was absent in slices from epileptic hippocampus and epileptic neocortex. PIN (10 μM) also reduced [3H]-NE release by 30% in non-epileptic neocortical slices and only by 5% in epileptic hippocampal slices. The blockade of voltage-gated calcium channels by ω-conotoxins MVIIA and MVIIC (0.1 μM) reduced [3H]-NE release in epileptic and non-epileptic neocortical slices to the same extend. The data show a marked reduction in K+-evoked [3H]-NE release by GBP and PIN in epileptic hippocampus and neocortex, suggesting an alteration of KATP channel function, whereas the effects of the calcium channel modulators ω-conotoxins MVIIA and MVIIC are similar in both epileptic and non-epileptic neocortex.