Chronic ethanol treatment alters ω-conotoxin and Bay K 8644 sensitive calcium channels in rat striatal synaptosomes

John J. Woodward, Tina Machu, Steven W. Leslie

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Two groups of adult Sprague-Dawley rats were maintained on a nutritionally complete liquid diet. In one group, 37% of the calories normally provided by dextrin were replaced with ethanol. Animals were maintained on this diet for eight weeks. The addition of ethanol (200 mM) in vitro significantly inhibited both calcium influx and dopamine release from control synaptosomes but did not alter calcium influx or dopamine release from synaptosomes isolated from ethanol-treated rats. The dihydropyridine calcium channel agonist Bay K 8644 (1 nM) significantly increased both calcium entry and dopamine release from control synaptosomes depolarized with 15 mM KCl. Bay K 8644 (1 nM) had no significant effect on either calcium entry or dopamine release in synaptosomes isolated from ethanol-treated animals. This loss of functional effect was accompanied by a slight (15%) but statistically insignificant increase in the binding of 3H-nitrendipine to striatal membranes from ethanol-treated rats as compared to control. The calcium-channel blocker, ω-conotoxin (500 nM) had no effect on voltage-dependent calcium uptake into synaptosomes prepared from control or ethanol-treated rats. Conotoxin (500 nM) inhibited the voltage-dependent release of endogenous dopamine from synaptosomes isolated from both groups by 36-44%. Ethanol (200 mM) added in vitro to control synaptosomes did not alter conotoxin's inhibition of dopamine release but completely abolished the ω-conotoxin-induced inhibition of dopamine release in synaptosomes isolated from ethanol-treated animals. These results suggest that DHP-sensitive and ω-conotoxin-sensitive calcium channels in rat brain respond differentially to chronic exposure to ethanol.

Original languageEnglish
Pages (from-to)279-284
Number of pages6
JournalAlcohol
Volume7
Issue number4
DOIs
StatePublished - 1990

Keywords

  • Alcohol
  • Bay K 8644
  • Calcium channels
  • Dihydropyridines
  • Dopamine release
  • Ethanol
  • Synaptosomes
  • ω-Conotoxin

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