Jpn. J. Pharmacol. 84 (4), 431-437 (2000)

Role of Ca²⁺ Mobilization in Muscarinic Receptor-Mediated Membrane Depolarization in Guinea Pig Ileal Smooth Muscle Cells

Toshihiro Unno¹, Tadafumi Inaba¹, Hidenori Ohashi¹, Tadashi Takewaki² and Seiichi Komori^1,*

¹Laboratory of Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, and ²Department of Pathogenetic Veterinary Science, United Graduate School, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
*Corresponding author.ﾊﾊFAX:+81-58-293-2942
E-mail: skomori@cc.gifu-u.ac.jp

Abstract: In single smooth muscle cells dispersed from guinea pig ileum, the muscarinic agonist carbachol (CCh) at 2ﾊmM produced an oscillatory or sustained type of depolarization and at 100ﾊmM, the latter type depolarization. Depletion of internal Ca²⁺ stores blocked the oscillatory response, but not the sustained responses to 2ﾊmM and 100ﾊmM CCh, although their decay after reaching the peak became faster. Blocking voltage-dependent Ca²⁺ channels (VDCCs) blocked both types of response to 2ﾊmM CCh, but only slowed the initial rising phase of 100ﾊmM CCh responses. Combination of Ca²⁺ store depletion and VDCC blockade abolished the responses to 2ﾊmM CCh again and decreased those to 100ﾊmM CCh in peak amplitude and persistency. Combination of Ca²⁺ store depletion with removal of extracellular Ca²⁺ markedly reduced or abolished the 100ﾊmM CCh responses. The results suggest that muscarinic depolarization of the ileal cells requires Ca²⁺ mobilization for its generation and persistence; at weak muscarinic stimulation, both Ca²⁺ entry via VDCCs and Ca²⁺ release from internal stores may contribute to the Ca²⁺ mobilization; and under strong muscarinic stimulation, Ca²⁺ entry pathways resistant to VDCC blockers may also contribute to it.

Keywords: Intestinal smooth muscle, Muscarinic receptor, Membrane potential, Ca²⁺ mobilization,
Ca²⁺ store