Bicarbonate contributes to GABAA receptor-mediated neuronal excitation in surgically resected human hypothalamic hamartomas.
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.
Kim
Do-Young
DY
Divisions of Pediatric Neurology and Neurology Research, Barrow Neurological Institute, St. Joseph's Hospital & Medical Center, Phoenix, AZ 85013, USA.
Fenoglio
Kristina A
KA
Kerrigan
John F
JF
Rho
Jong M
JM
D000293:Adolescent; D001639:Bicarbonates / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D004594:Electrophysiology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D006096:Gramicidin; D006222:Hamartoma / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D007029:Hypothalamic Neoplasms / Q000150:complications / Q000503:physiopathology*; D007223:Infant; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011963:Receptors, GABA-A / Q000502:physiology*; D012640:Seizures / Q000209:etiology
D001639:Bicarbonates; D020746:Calcium Channels, L-Type; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D006096:Gramicidin; D009118:Muscimol; D002118:Calcium