Inhibition of trigeminovascular dural nociceptive afferents by Ca(2+)-activated K(+) (MaxiK/BK(Ca)) channel opening

Simon Akerman, Philip R Holland, Michele P Lasalandra, Peter J Goadsby

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Migraine is an episodic brain disorder with a significant morbidity. It is thought that activation of trigeminal afferents innervating the dura mater and large cerebral blood vessels is involved in the expression of the disorder. The selective large conductance calcium-activated potassium channels, the BKCa or MaxiK channels, are intrinsic membrane proteins that are widely distributed in the brain. These channels are thought to be involved in controlling neuronal excitability and perhaps transmitter release, possibly in the trigeminocervical complex. We sought to investigate the role of MaxiK/BKCa channels opening in several models of trigeminovascular nociception using NS1619, a benzimidazolone analogue. Intravenously administered NS1619 (10 mg kg−1) was able to inhibit neurogenic dural vasodilation (F4,20 = 19.23, P < 0.05, n = 6). NS1619 (intravenous) was not able to inhibit Aδ-fiber (F3.01,18.06 = 0.79, P = 0.52) or C-fiber (F3.14,18.84 = 0.76, P = 0.54) afferents in the trigeminal nucleus caudalis and C1 region of the dorsal horn after dural electrical stimulation, but it was able to inhibit Aδ-fiber afferents after iontophoretic application of NS1619 (t5 = 3.23, P < 0.05, n = 6) after 5 min. Iontophoresed NS1619 was also able to inhibit l-glutamate induced firing in the trigeminocervical complex, in a dose-dependent manner (F3,54 = 3.06, P < 0.05). The data taken together indicate that the MaxiK/BKCa channel may represent a novel therapeutic target in migraine.
Original languageEnglish
Article numberN/A
Pages (from-to)128-136
Number of pages9
JournalPain
Volume151
Issue number1
DOIs
Publication statusPublished - Oct 2010

Keywords

  • Action Potentials
  • Analysis of Variance
  • Animals
  • Benzimidazoles
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Dura Mater
  • Electric Stimulation
  • Glutamic Acid
  • Iontophoresis
  • Large-Conductance Calcium-Activated Potassium Channels
  • Male
  • Meningeal Arteries
  • Neural Inhibition
  • Potassium Channel Blockers
  • Rats
  • Rats, Sprague-Dawley
  • Sensory Receptor Cells
  • Time Factors
  • Trigeminal Caudal Nucleus
  • Trigeminal Nerve
  • Vasodilation

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