Tetrahydroberberine blocks ATP-sensitive potassium channels in dopamine neurons acutely-dissociated from rat substantia nigra pars compacta

Chen Wu, Kechun Yang, Qiang Liu, Matoko Wakui, Guo zhang Jin, Xuechu Zhen, Jie Wu

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Tetrahydroberberine (THB) exhibits neuroprotective effects but its targets and underlying mechanisms are largely unknown. Emerging evidence indicates that ATP-sensitive potassium (KATP) channels in the substantia nigra pars compacta (SNc) promote Parkinson disease (PD) pathogenesis, thus blocking KATP channels may protect neurons against neuronal degeneration. In the present study, we tested a hypothesis that THB blocks KATP channels in dopaminergic (DA) neurons acutely dissociated from rat SNc. Using perforated patch-clamp recording in current-clamp mode, the functional KATP channels can be opened by persistent perfusion of rotenone, an inhibitor of complex I of the mitochondrial respiratory chain. Bath-application of THB reversibly blocks opened KATP channels in a concentration-dependent manner, which is comparable to a classical KATP channel blocker, Tol. Compared to THB analogs, l-stepholidine (l-SPD) or l-tetrahydropalmatine (l-THP), THB exhibits more profound blockade in KATP channels. In addition, exposure of THB alone to the recorded neuron increases action potential firing, and THB also restores rotenone-induced membrane hyperpolarization in the presence of dopamine D2 receptor antagonist (sulpiride), suggesting that THB exhibits an excitatory effect on SNc DA neurons through the block of KATP channels. Collectively, the blockade of neuronal KATP channels by THB in SNc DA neurons is a novel pharmacological mechanism of THB, which may contribute to its neuroprotective effects in PD.

Original languageEnglish (US)
Pages (from-to)567-572
Number of pages6
JournalNeuropharmacology
Volume59
Issue number7-8
DOIs
StatePublished - Dec 2010
Externally publishedYes

Keywords

  • ATP-sensitive K channel
  • Dopaminergic neurons
  • Parch-clamp
  • Rotenone
  • Substantia nigra compacta
  • Tetrahydroberberine

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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