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 Komori1,*

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.╩╩FAX:+81-58-293-2942

Abstract: In single smooth muscle cells dispersed from guinea pig ileum, the muscarinic agonist carbachol (CCh) at 2╩mM produced an oscillatory or sustained type of depolarization and at 100╩mM, the latter type depolarization. Depletion of internal Ca2+ stores blocked the oscillatory response, but not the sustained responses to 2╩mM and 100╩mM CCh, although their decay after reaching the peak became faster. Blocking voltage-dependent Ca2+ channels (VDCCs) blocked both types of response to 2╩mM CCh, but only slowed the initial rising phase of 100╩mM CCh responses. Combination of Ca2+ store depletion and VDCC blockade abolished the responses to 2╩mM CCh again and decreased those to 100╩mM CCh in peak amplitude and persistency. Combination of Ca2+ store depletion with removal of extracellular Ca2+ markedly reduced or abolished the 100╩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

Copyrightę The Japanese Pharmacological Society 2000

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