title: Effects of Ca2+ channel antagonists on nerve stimulation-induced and ischemia-induced myocardial interstitial acetylcholine release in cats.
abstract: Although an axoplasmic Ca(2+) increase is associated with an exocytotic acetylcholine (ACh) release from the parasympathetic postganglionic nerve endings, the role of voltage-dependent Ca(2+) channels in ACh release in the mammalian cardiac parasympathetic nerve is not clearly understood. Using a cardiac microdialysis technique, we examined the effects of Ca(2+) channel antagonists on vagal nerve stimulation- and ischemia-induced myocardial interstitial ACh releases in anesthetized cats. The vagal stimulation-induced ACh release [22.4 nM (SD 10.6), n = 7] was significantly attenuated by local administration of an N-type Ca(2+) channel antagonist omega-conotoxin GVIA [11.7 nM (SD 5.8), n = 7, P = 0.0054], or a P/Q-type Ca(2+) channel antagonist omega-conotoxin MVIIC [3.8 nM (SD 2.3), n = 6, P = 0.0002] but not by local administration of an L-type Ca(2+) channel antagonist verapamil [23.5 nM (SD 6.0), n = 5, P = 0.758]. The ischemia-induced myocardial interstitial ACh release [15.0 nM (SD 8.3), n = 8] was not attenuated by local administration of the L-, N-, or P/Q-type Ca(2+) channel antagonists, by inhibition of Na(+)/Ca(2+) exchange, or by blockade of inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] receptor but was significantly suppressed by local administration of gadolinium [2.8 nM (SD 2.6), n = 6, P = 0.0283]. In conclusion, stimulation-induced ACh release from the cardiac postganglionic nerves depends on the N- and P/Q-type Ca(2+) channels (with a dominance of P/Q-type) but probably not on the L-type Ca(2+) channels in cats. In contrast, ischemia-induced ACh release depends on nonselective cation channels or cation-selective stretch activated channels but not on L-, N-, or P/Q type Ca(2+) channels, Na(+)/Ca(2+) exchange, or Ins(1,4,5)P(3) receptor-mediated pathway.
authors.affiliation: Dept. of Cardiovascular Dynamics, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. torukawa@res.ncvc.go.jp
authors.forename: Toru
authors.initials: T
authors.lastname: Kawada
authors.forename: Toji
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Akiyama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Uemura
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kamiya
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shishido
authors.forename: Hidezo
authors.initials: H
authors.lastname: Mori
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugimachi
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000187:drug effects; D002415:Cats; D020916:Conotoxins / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D017551:Microdialysis / Q000379:methods; D017202:Myocardial Ischemia / Q000209:etiology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009417:Nerve Tissue / Q000187:drug effects*; D014630:Vagus Nerve / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020916:Conotoxins; D005682:Gadolinium; D000109:Acetylcholine