Bicarbonate contributes to GABAA receptor-mediated neuronal excitation in surgically resected human hypothalamic hamartomas

Epilepsy Res. 2009 Jan;83(1):89-93. doi: 10.1016/j.eplepsyres.2008.09.008. Epub 2008 Nov 20.

Abstract

The role of bicarbonate (HCO(3)(-)) in GABA(A) receptor-mediated depolarization of human hypothalamic hamartoma (HH) neurons was investigated using cellular electrophysiological and calcium imaging techniques. Activation of GABA(A) receptors with muscimol (30 microM) provoked neuronal excitation in over 70% of large (18-22 microM) HH neurons in HCO(3)(-) buffer. Subsequent perfusion of HCO(3)(-)-free HEPES buffer produced partial suppression of muscimol-induced excitation. Additionally, 53% of large HH neurons under HCO(3)(-)-free conditions exhibited reduced intracellular calcium accumulation by muscimol. These results suggest that HCO(3)(-) efflux through GABA(A) receptors on a subpopulation of large HH neurons may contribute to membrane depolarization and subsequent activation of L-type calcium channels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Bicarbonates / metabolism*
  • Calcium / metabolism
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / physiology
  • Child
  • Child, Preschool
  • Electrophysiology
  • Female
  • GABA Agonists / pharmacology
  • GABA-A Receptor Agonists
  • Gramicidin
  • Hamartoma / complications
  • Hamartoma / physiopathology*
  • Humans
  • Hypothalamic Neoplasms / complications
  • Hypothalamic Neoplasms / physiopathology*
  • Infant
  • Male
  • Muscimol / pharmacology
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Receptors, GABA-A / physiology*
  • Seizures / etiology

Substances

  • Bicarbonates
  • Calcium Channels, L-Type
  • GABA Agonists
  • GABA-A Receptor Agonists
  • Receptors, GABA-A
  • Gramicidin
  • Muscimol
  • Calcium