Increased sensitivity to nicotine-induced seizures in mice heterozygous for the L250T mutation in the alpha7 nicotinic acetylcholine receptor.

Abstract

alpha7 Nicotinic acetylcholine receptors (nAChRs) are sparsely distributed throughout the peripheral and central nervous systems. Several studies have suggested that central alpha7 nicotinic receptors may influence sensitivity to nicotine-induced seizures in mice. In order to investigate the effect of alpha7 nAChRs on seizure sensitivity, we tested heterozygous mice with a threonine for leucine substitution at position 250 (L250T) within the channel domain, which is known to increase current amplitude and decreases desensitization of the channel. We show that administration of low doses of nicotine to these mutant mice increased the sensitivity to nicotine-induced seizures and the mortality rate. EEG recordings showed high amplitude rhythmic activity during tonic-clonic seizures. Pretreatment with the alpha7 nicotinic receptor antagonist methyllycaconitine inhibited the seizures induced by nicotine. These findings further suggest an important role for alpha7 nAChRs in the nicotine-induced seizures model of epilepsy.

• Authors: Ziv Gil, Ram A Sack, Merav Kedmi, Alon Harmelin, Avi Orr-Urtreger
• Journal: Neuroreport (Neuroreport) Vol. 13 Issue 2 Pg. 191-6 (Feb 11 2002) ISSN: 0959-4965 [Print] England
• PMID: 11893908 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chrna7 protein, mouse
• Ganglionic Stimulants
• Receptors, Nicotinic
• alpha7 Nicotinic Acetylcholine Receptor
• Nicotine

Topics

• Animals
• Behavior, Animal (drug effects)
• Electroencephalography
• Ganglionic Stimulants (pharmacology, poisoning)
• Genetic Predisposition to Disease
• Heterozygote
• Mice
• Mice, Inbred C57BL
• Mortality
• Mutation (physiology)
• Nicotine (pharmacology, poisoning)
• Receptors, Nicotinic (genetics)
• Reference Values
• Seizures (chemically induced, genetics, physiopathology)
• alpha7 Nicotinic Acetylcholine Receptor