Suppression of the hyperpolarization-activated inward current contributes to the inhibitory actions of propofol on rat CA1 and CA3 pyramidal neurons

Hitoshi Higuchi, Makoto Funahashi, Takuya Miyawaki, Yoshihiro Mitoh, Atsushi Kohjitani, Masahiko Shimada, Ryuji Matsuo

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Intracellular and field potential recordings were taken from the hippocampal CA1 and CA3 neurons in rat brain slices to investigate the effects of 2,6 di-isopropylphenol (propofol) on the neuronal excitability during GABAA-C1 channel blockade by picrotoxin (100 μM). Propofol produced a membrane hyperpolarization and an inhibition of the magnitude of the 'voltage sag' that was mediated by the activation of a hyperpolarization-activated inward current (IH). Propofol (> 100 μM) decreased the spontaneous discharge rate of epileptiform burst responses in CA1 neurons up to 38±6% of the control level. Propofol also markedly reduced the duration of both spontaneous and evoked epileptiform burst responses. A propofol-induced decrease in the spontaneous discharge rate in CA3 neurons was coincident with that in CA1 neurons. The effects of propofol on the membrane potential and spontaneous discharge rate but not on the duration of burst responses were duplicated by ZD7288 (potent selective antagonist for IH channels), indicating that the blockade of IH significantly contributes to reduction of cell's excitability. The present study suggests that various actions including suppressive effects on IH contribute to the anesthetic and anti-convulsant properties of propofol.

Original languageEnglish
Pages (from-to)459-472
Number of pages14
JournalNeuroscience Research
Issue number4
Publication statusPublished - Apr 1 2003



  • Brain slice
  • I
  • Propofol
  • Rats

ASJC Scopus subject areas

  • Neuroscience(all)

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