Noradrenergic blockade prevents attacks in a model of episodic dysfunction caused by a channelopathy

Brandy E. Fureman, Ellen J. Hess

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Episodic neurological dysfunction often results from ion channel gene mutations. Despite knowledge of the mutations, the factors that precipitate attacks in channelopathies are not clear. In humans, mutations of the calcium channel gene CACNA1A are associated with attacks of neurological dysfunction in familial hemiplegic migraine and episodic ataxia type-2. In tottering mice, a mutation in the same gene causes attacks resembling paroxysmal dyskinesia. Stress, a trigger associated with human episodic disorders, reliably elicits attacks in tottering mice. Because noradrenergic neurotransmission is critical to the stress response and because noradrenergic hyperinnervation is observed in tottering mice, the role of norepinephrine in stress-induced attacks was investigated. Drugs that act at α-adrenergic receptors to block noradrenergic transmission prevented attacks. However, agents that facilitate noradrenergic neurotransmission failed to induce attacks. These results suggest that, while noradrenergic neurotransmission may be necessary for attacks, an increase in norepinephrine is not sufficient to induce attacks.

Original languageEnglish (US)
Pages (from-to)227-232
Number of pages6
JournalNeurobiology of Disease
Issue number2
StatePublished - Nov 2005


  • Adrenergic
  • Animal model
  • Calcium channel
  • Dystonia
  • Episodic ataxia
  • Familial hemiplegic migraine
  • Mutation
  • Paroxysmal dyskinesia
  • Tottering

ASJC Scopus subject areas

  • Neurology


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