Inhibition by bis(7)-tacrine of native delayed rectifier and KV1.2 encoded potassium channels

Hui Nie, Wen Jing Yu, Xiang Yuan Li, Chun Hua Yuan, Yuan-Ping Pang, Chao Ying Li, Yi Fan Han, Zhi Wang Li

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Bis(7)-tacrine [bis(7)-tetrahydroaminacrine] acts as an AChE inhibitor and also exerts modulatory effects on many ligand-gated ion channels and voltage-gated Ca2+ and K+ channels. It has been reported previously that tacrine and some other AChE inhibitors suppressed IK(A) in central and peripheral neurons. The present study aimed to explore whether bis(7)-tacrine could modulate the function of native delayed rectifier potassium channels in DRG neurons and KV1.2 encoded potassium channels expressed in oocytes. We found that both delayed rectifier potassium currents (IK(DR)) in rat DRG neurons and the currents recorded from oocytes expressing KV1.2 (IK (KV 1.2)) were suppressed by bis(7)-tacrine, the potency of which was two orders greater than that of tacrine. The IC50 values for bis(7)-tacrine and tacrine inhibition of IK(KD) in DRG neurons were 0.72 ± 0.05 and 58.3 ± 3.7 μM, respectively; while the two agents inhibited IK (KV 1.2) in oocytes with an IC50 of 0.24 ± 0.06 and 102.1 ± 21.5 μM, respectively. The possible mechanism for bis(7)-tacrine inhibition of IK(A) and IK (KV 1.2) was identified as the suppression of their activation, inactivation.

Original languageEnglish (US)
Pages (from-to)108-113
Number of pages6
JournalNeuroscience Letters
Volume412
Issue number2
DOIs
StatePublished - Jan 29 2007

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Potassium Channels
Tacrine
Diagnosis-Related Groups
Oocytes
Neurons
Inhibitory Concentration 50
Delayed Rectifier Potassium Channels
Ligand-Gated Ion Channels
Voltage-Gated Potassium Channels
Potassium
1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine

Keywords

  • Bis(7)-tacrine
  • Delayed rectifier K channel
  • Drug for treatment of AD
  • Expression
  • K1.2 encoded potassium channel
  • Multi-target
  • Oocyte of Xenopus laevis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Inhibition by bis(7)-tacrine of native delayed rectifier and KV1.2 encoded potassium channels. / Nie, Hui; Yu, Wen Jing; Li, Xiang Yuan; Yuan, Chun Hua; Pang, Yuan-Ping; Li, Chao Ying; Han, Yi Fan; Li, Zhi Wang.

In: Neuroscience Letters, Vol. 412, No. 2, 29.01.2007, p. 108-113.

Research output: Contribution to journalArticle

Nie, Hui ; Yu, Wen Jing ; Li, Xiang Yuan ; Yuan, Chun Hua ; Pang, Yuan-Ping ; Li, Chao Ying ; Han, Yi Fan ; Li, Zhi Wang. / Inhibition by bis(7)-tacrine of native delayed rectifier and KV1.2 encoded potassium channels. In: Neuroscience Letters. 2007 ; Vol. 412, No. 2. pp. 108-113.
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