Volatile anesthetic isoflurane inhibits LTP induction of hippocampal CA1 neurons through a4ß2 nAChR subtype-mediated mechanisms.

Annales francaises d'anesthesie et de reanimation

PubMedID: 24011619

Piao MH, Liu Y, Wang YS, Qiu JP, Feng CS. Volatile anesthetic isoflurane inhibits LTP induction of hippocampal CA1 neurons through a4ß2 nAChR subtype-mediated mechanisms. Ann Fr Anesth Reanim. 2013;.
BACKGROUND AND PURPOSE
Volatile anesthetic isoflurane contributes to postoperative cognitive dysfunction and inhibition of long-term potentiation (LTP), a synaptic model of learning and memory, but the mechanisms are uncertain. Central neuronal a4ß2 subtype nicotinic acetylcholine receptors (nAChRs) are involved in the induction of LTP in the hippocampus. Isoflurane inhibits a4ß2 nAChRs at concentrations lower than those used for anesthesia. Therefore, we hypothesized that isoflurane-inhibited LTP induction of hippocampal CA1 neurons via a4ß2 nAChRs subtype inhibition.

METHODS
Transverse hippocampal slices (400µm thick) were obtained from male rats (6-8 weeks old). Population spikes were evoked using extracellular electrodes by electrical stimulation of the Schaffer collateral-commissural pathway of rat hippocampal slices. LTP was induced using high frequency stimulation (HFS; 100Hz, 1s). Clinically relevant concentrations (0.125-0.5mM) of isoflurane with or without nicotine (nAChRs agonist), mecamylamine (nAChRs antagonist), 3-[2(S)-2-azetidinylmethoxy] pyridine (A85380) and epibatidine (a4ß2 nAChRs agonist), dihydro ß erythroidine (DHßE) (a4ß2 nAChRs antagonist) were added to the perfusion solution 20min before HFS to test their effects on LTP by HFS respectively.

RESULTS
A brief HFS induced stable LTP in rat hippocampal slices, but LTP was significantly inhibited in the presence of isoflurane at concentrations of 0.125-0.5mM. The inhibitive effect of isoflurane on LTP was not only reversible and could be prevented by nAChRs agonist nicotine and a4ß2 nAChRs agonist A85380 and epibatidine, but also mimicked and potentiated by nAChRs antagonist mecamylamine and a4ß2 nAChRs antagonist DHßE.

CONCLUSIONS
Inhibition of a4ß2 nAChRs subtype of hippocampus participates in isoflurane-mediated LTP inhibition.