title: Amitriptyline modulates calcium currents and intracellular calcium concentration in mouse trigeminal ganglion neurons.
abstract: Migraine is increasingly recognized as a channelopathy, and abnormalities of voltage-activated ionic channels could represent the molecular basis for the altered neuronal functioning. The high-voltage-activated (HVA) Ca(2+) channels in the trigeminovascular system play a role in the pathophysiology of migraine. In the present study, effects of amitriptyline (AMT), a commonly used migraine prophylactic drug, on the HVA calcium currents (I(Ca)) were examined in mouse trigeminal ganglion neurons using whole-cell patch clamp technique. AMT produced concentration- and use-dependent inhibition of HVA I(Ca). Bath application of GÖ-6983 (a selective protein kinase C inhibitor) or H89 (a protein kinase A inhibitor) did not reduce the AMT-induced inhibition of HVA I(Ca). A similar inhibition was observed when calcium imaging was used to directly monitor the effects of AMT on KCl-induced increments of intracellular Ca(2+) concentration ([Ca(2+)](i)). By blocking HVA Ca(2+) channels and Ca(2+) entry into cells, AMT could prevent the release of neurotransmitters and help restore the neuronal threshold for excitation. Our findings suggest interesting therapeutic mechanisms for AMT in migraine prevention.
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, Guangzhou Street 300, Nanjing, Jiangsu Province, 210029, PR China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Wu
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.forename: LanYun
authors.initials: L
authors.lastname: Yan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
authors.forename: Qi
authors.initials: Q
authors.lastname: Wan
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism
chemical_list: D018712:Analgesics, Non-Narcotic; D015220:Calcium Channels; D000639:Amitriptyline; D002118:Calcium