Effects of Ca2+ channel antagonists on nerve stimulation-induced and ischemia-induced myocardial interstitial acetylcholine release in cats

Toru Kawada, Toji Yamazaki, Tsuyoshi Akiyama, Kazunori Uemura, Atsunori Kamiya, Toshiaki Shishido, Hidezo Mori, Masaru Sugimachi

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9 Citations (Scopus)


Although an axoplasmic Ca2+ increase is associated with an exocytotic acetylcholine (ACh) release from the parasympathetic postganglionic nerve endings, the role of voltage-dependent Ca2+ channels in ACh release in the mammalian cardiac parasympathetic nerve is not clearly understood. Using a cardiac microdialysis technique, we examined the effects of Ca2+ 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 Ca2+ channel antagonist ω-conotoxin GVIA [11.7 nM (SD 5.8), n = 7, P = 0.0054], or a P/Q-type Ca2+ channel antagonist ω-conotoxin MVIIC [3.8 nM (SD 2.3), n = 6, P = 0.0002] but not by local administration of an L-type Ca2+ 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 Ca2+ channel antagonists, by inhibition of Na +/Ca2+ exchange, or by blockade of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] 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 Ca2+ channels (with a dominance of P/Q-type) but probably not on the L-type Ca2+ 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 Ca2+ channels, Na+/Ca 2+ exchange, or Ins(1,4,5)P3 receptor-mediated pathway.

Original languageEnglish
Pages (from-to)H2187-H2191
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number5
Publication statusPublished - 2006
Externally publishedYes


  • Cardiac microdialysis
  • KB-R7943
  • Vagal stimulation
  • Verapamil
  • ω-conotoxin GVIA
  • ω-conotoxin MVIIC

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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