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

Kawada, Toru, Toji Yamazaki, Tsuyoshi Akiyama, Kazunori Uemura, Atsunori Kamiya, Toshiaki Shishido, Hidezo Mori, and Masaru Sugimachi. Effects of Ca channel antagonists on nerve stimulation-induced and ischemia-induced myocardial interstitial acetylcholine release in cats. Am J Physiol Heart Circ Physiol 291: H2187–H2191, 2006. First published June 9, 2006; doi:10.1152/ajpheart.00175.2006.—Although an axoplasmic Ca increase is associated with an exocytotic acetylcholine (ACh) release from the parasympathetic postganglionic nerve endings, the role of voltage-dependent Ca 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 channel antagonists on vagal nerve stimulationand 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 channel antagonist -conotoxin GVIA [11.7 nM (SD 5.8), n 7, P 0.0054], or a P/Q-type Ca channel antagonist -conotoxin MVIIC [3.8 nM (SD 2.3), n 6, P 0.0002] but not by local administration of an L-type Ca 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 channel antagonists, by inhibition of Na /Ca 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 Nand P/Q-type Ca channels (with a dominance of P/Q-type) but probably not on the L-type Ca 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 channels, Na /Ca exchange, or Ins(1,4,5)P3 receptor-mediated pathway.