Chronic ethanol treatment alters AMPA-induced calcium signals in developing Purkinje neurons

Brain Res. 1999 May 1;826(2):270-80. doi: 10.1016/s0006-8993(99)01309-8.

Abstract

Cerebellar Purkinje neurons developing in culture were treated chronically with 30 mM (140 mg%; 3-11 days in vitro) ethanol to study the actions of prolonged ethanol exposure on responses to exogenous application of AMPA, a selective agonist at the AMPA subtype of ionotropic glutamate receptors. There was no consistent difference between control and chronic ethanol-treated neurons in resting membrane potential, input resistance, or the amplitude or duration of the membrane responses to AMPA (1 or 5 microM applied by brief microperfusion) as measured using the nystatin patch method of whole cell recording. In additional studies, the Ca2+ signal to AMPA was examined using the Ca2+ sensitive dye fura-2. The mean peak Ca2+ signal elicited by 5 microM AMPA was enhanced in the dendritic region (but not the somatic region) of chronic ethanol-treated Purkinje neurons compared to control neurons. In contrast, there was no difference between control and chronic ethanol-treated neurons in the peak amplitude of the Ca2+ signal to 1 microM AMPA, whereas the recovery of the Ca2+ signals was more rapid in both somatic and dendritic regions of ethanol-treated neurons. Resting Ca2+ levels in the somatic and dendritic regions were similar between control and ethanol-treated neurons. These data show that the membrane and Ca2+ responses to AMPA in Purkinje neurons are differentially affected by prolonged ethanol exposure during development. Moreover, chronic ethanol exposure produces a selective enhancement of AMPA-evoked dendritic Ca2+ signals under conditions reflecting intense activation (i.e., 5 microM AMPA), whereas both somatic and dendritic Ca2+ signals are attenuated with smaller levels of activation (i.e., 1 microM AMPA). Because Ca2+ is an important regulator of numerous intracellular functions, chronic ethanol exposure during development could produce widespread changes in the development and function of the cerebellum.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Signaling / drug effects*
  • Cell Division / drug effects
  • Cells, Cultured
  • Central Nervous System Depressants / pharmacology*
  • Cerebellum / cytology
  • Dendrites / drug effects
  • Dendrites / metabolism
  • Electrophysiology
  • Ethanol / pharmacology*
  • Excitatory Amino Acid Agonists / pharmacology*
  • Membrane Potentials / drug effects
  • Purkinje Cells / cytology
  • Purkinje Cells / drug effects*
  • Purkinje Cells / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Tetrodotoxin / pharmacology
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology*

Substances

  • Central Nervous System Depressants
  • Excitatory Amino Acid Agonists
  • Ethanol
  • Tetrodotoxin
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Calcium