The opening effect of pregabalin on ATP-sensitive potassium channels in differentiated hippocampal neuron-derived H19-7 cells

Chin Wei Huang, Chao Ching Huang, Sheng Nan Wu

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25 Citations (Scopus)

Abstract

Purpose: Adenosine triphosphate (ATP)-sensitive K+ (K ATP) channels can couple an intracellular metabolic state to an electrical activity, which is important in the control of neuronal excitability and seizure propagation. We investigated whether the newer antiepileptic drug, pregabalin (PGB), could exert effects on KATP channels in differentiated hippocampal neuron-derived H19-7 cells. Methods: The inside-out configuration of the patch-clamp technique was used to investigate K ATP channel activities in H19-7 cells in the presence of PGB. Effects of various compounds known to alter KATP channel activities were compared. Results: The activity of KATP channels in these cells was characterized. The single-channel conductance from a linear current-voltage relation was 78 ± 2 pS (n = 8) with a reversal potential of 63 ± 2 mV (n = 8), similar to that of KATP channels reported in pancreatic β cells. 2,4-Dinitrophenol activated channel activity, but the further addition of glucose (20 mM) or glibenclamide (30 μM) could offset these increments. PGB significantly opened these KATP channel activities in a concentration-dependent fashion with a median effective concentration (EC50) value of 18 μM. A significant increase was noted in the mean open lifetime of KATP channels in the presence of PGB (1.71 ± 0.04 to 5.62 ± 0.04 ms). Conclusions: This study suggests that in differentiated hippocampal neuron-derived H19-7 cells, the opening effect on KATP channels could be one of the underlying mechanisms of PGB in the reduction of neuronal excitability.

Original languageEnglish
Pages (from-to)720-726
Number of pages7
JournalEpilepsia
Volume47
Issue number4
DOIs
Publication statusPublished - Apr 2006
Externally publishedYes

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Keywords

  • ATP-sensitive potassium channels
  • Hippocampus
  • Pregabalin

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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