Role of Ca2+ mobilization in muscarinic receptor-mediated membrane depolarization in guinea pig ileal smooth muscle cells

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