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Related Experiment Videos

Ethanol modulates calmodulin-dependent Ca(2+)-activated ATPase in synaptic plasma membranes

Z Iqbal1, P Y Sze

  • 1Department of Pharmacology and Molecular Biology, Chicago Medical School, Illinois 60064.

Neurochemical Research
|April 1, 1994
PubMed
Summary

Ethanol inhibits brain calmodulin-dependent Ca(2+)-ATPase in normal rats, but chronic exposure leads to resistance. This resistance involves altered enzyme affinity and membrane properties, potentially affecting synaptic activity.

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Pharmacology

Background:

  • The calmodulin-dependent Ca(2+)-ATPase (CaM-Ca(2+)-ATPase) in synaptic plasma membranes (SPM) regulates intracellular calcium levels.
  • Dysregulation of Ca(2+) homeostasis is implicated in ethanol's neurotoxic effects.

Purpose of the Study:

  • To investigate the in vitro effects of ethanol on CaM-Ca(2+)-ATPase activity in SPM from normal and chronically ethanol-treated rats.
  • To elucidate the mechanisms underlying ethanol-induced changes in enzyme activity and membrane properties.

Main Methods:

  • Preparation of synaptic plasma membranes (SPM) from rat brains.
  • Enzymatic assays to measure Ca(2+)-ATPase activity.
  • Lineweaver-Burk and Arrhenius analyses to determine kinetic parameters and membrane lipid properties.

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Main Results:

  • In vitro ethanol (50-200 mM) inhibited CaM-Ca(2+)-ATPase activity in SPM from normal rats by decreasing enzyme affinity for calmodulin.
  • Ethanol treatment shifted the membrane lipid transition temperature to lower values.
  • SPM from chronically ethanol-treated rats exhibited resistance to ethanol's inhibitory effects, showing higher enzyme affinity for calmodulin and higher transition temperatures.

Conclusions:

  • Chronic ethanol exposure induces adaptive changes in SPM CaM-Ca(2+)-ATPase, conferring resistance to ethanol's inhibitory actions.
  • These adaptations involve alterations in enzyme kinetics and membrane fluidity.
  • Modulation of this critical calcium pump by ethanol may contribute to altered synaptic function in chronic alcoholism.