Suppression of the hyperpolarization-activated inward current contributes to the inhibitory actions of propofol on rat CA1 and CA3 pyramidal neurons.
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 GABA(A)-C1 channel blockade by picrotoxin (100 microM). 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 (I(H)). Propofol (>100 microM) 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 I(H) channels), indicating that the blockade of I(H) significantly contributes to reduction of cell's excitability. The present study suggests that various actions including suppressive effects on I(H) contribute to the anesthetic and anti-convulsant properties of propofol.
Higuchi
Hitoshi
H
Department of Dental Anesthesiology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8525, Japan. higuti@md.okayama-u.ac.jp
Funahashi
Makoto
M
Miyawaki
Takuya
T
Mitoh
Yoshihiro
Y
Kohjitani
Atsushi
A
Shimada
Masahiko
M
Matsuo
Ryuji
R
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D008839:Microelectrodes; D009924:Organ Culture Techniques; D010852:Picrotoxin / Q000494:pharmacology; D015221:Potassium Channels; D015742:Propofol / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018686:Anesthetics, Intravenous; D054815:Cyclic Nucleotide-Gated Cation Channels; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D010852:Picrotoxin; D015221:Potassium Channels; D015742:Propofol