Tetrahydroberberine inhibits acetylcholine-induced K+ current in acutely dissociated rat hippocampal CA1 pyramidal neurons

Jie Wu, Guo Zhang Jin

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The effects of a novel chemical type of dopamine receptor antagonist, the tetrahydroprotoberberine analogs (THPBs), on acetylcholine (ACh)-induced current were studied in freshly dissociated pyramidal neurons from rat hippocampal CA1 area using the nystatin perforated patch-clamp recording technique. Under voltage clamp conditions, the ACh-induced outward current (I(ACh)) is sensitive to the muscarinic receptor antagonist, atropine and the K+ channel blocker, TEA. The reversal potential of I(ACh) (-84.1 ± 0.8 mV) is close to the K+ equilibrium potential, indicating that the I(ACh) is mediated by a muscarinic receptor, and is carried mainly by K+. Tetrahydroberberine (THB) markedly reduced the I(ACh) while its chemical analogs, l-stepholidine (l-SPD) or l-tetrahydropalmatine (l-THP), had little effect on the I(ACh). The half-maximal inhibitory concentration (IC50) of THB was 1.3 x 10-5 M for a 10-5 M ACh-induced I(ACh). THB suppressed the maximum of the ACh concentration-response curve without shifting the Hill coefficient, indicating a non-competitive inhibition. It is concluded that THB non-competitively inhibits the ACh-induced K+ current in a concentration-dependent manner, and that this inhibitory effect provides further evidence that THB plays its pharmacological roles in the central nervous system by effects other than through blockade of dopamine receptors.

Original languageEnglish (US)
Pages (from-to)115-118
Number of pages4
JournalNeuroscience Letters
Volume222
Issue number2
DOIs
StatePublished - Jan 31 1997
Externally publishedYes

Keywords

  • acetylcholine
  • dissociated neurons
  • K current
  • patch-clamp
  • rat hippocampus
  • tetrahydroberberine

ASJC Scopus subject areas

  • Neuroscience(all)

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