Triggers of paroxysmal dyskinesia in the calcium channel mouse mutant tottering.
Mutations in ion channels, or channelopathies, often lead to neurological disorders in which normal behavior is interrupted by attacks of debilitating symptoms such as pain, weakness or abnormal motor control. Attacks are often precipitated by similar stimuli, including stress, caffeine, ethanol, exercise or fatigue. The tottering mouse inherits a mutation in P/Q-type calcium channels and reliably exhibits attacks of abnormal movements, or dyskinesia. To determine if this mouse mutant is an appropriate model to study episodic neurological disorders, tottering mice were exposed to different environmental conditions or drugs known to precipitate attacks in humans. Stress, caffeine and ethanol all reliably induced attacks in tottering mice. Since calcium influx has previously been implicated in stress-induced tottering mouse attacks, the L-type calcium channel antagonist, nimodipine, and the NMDA receptor antagonist, MK 801, were tested for their ability to prevent attacks caused by caffeine or ethanol administration. Nimodipine blocked both caffeine- and ethanol-induced attacks, while MK 801 was effective against stress- and caffeine-induced attacks. These results support a common role for excess neuronal excitability and increased calcium influx in attacks triggered by diverse agents. Together, these results suggest that the tottering mouse is a novel model to investigate triggers of episodic neurological disorders.
Fureman
Brandy E
BE
Department of Neurology, Johns Hopkins University School of Medicine, Meyer Room 6-181, 600 North Wolfe Street, Baltimore, MD 21287, USA.
Jinnah
H A
HA
Hess
Ellen J
EJ
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000235:genetics*; D020013:Calcium Signaling / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002819:Chorea / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004777:Environment; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008029:Lighting; D051379:Mice; D008818:Mice, Neurologic Mutants; D009553:Nimodipine / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012149:Restraint, Physical; D012640:Seizures / Q000503:physiopathology; D013315:Stress, Psychological / Q000523:psychology
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D002110:Caffeine; D009553:Nimodipine; D016291:Dizocilpine Maleate