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 muscarin ic agonist carbachol (CCh) at 2 muM produced an oscillatory or sustained ty pe of depolarization and at 100 muM, the latter type depolarization. Deplet ion of internal Ca2+ stores blocked the oscillatory response, but not the s ustained responses to 2 muM and 100 muM CCh, although their decay after rea ching the peak became faster. Blocking voltage-dependent Ca2+ channels (VDC Cs) blocked both types of response to 2 muM CCh, but only slowed the initia l rising phase of 100 muM CCh responses. Combination of Ca2+ store depletio n and VDCC blockade abolished the responses to 2 muM CCh again and decrease d those to 100 muM CCh in peak amplitude and persistency. Combination of Ca 2+ store depletion with removal of extracellular Ca2+ markedly reduced or a bolished the 100 muM CCh responses. The results suggest that muscarinic dep olarization of the ileal cells requires Ca2+ mobilization for its generatio n and persistence; at weak muscarinic stimulation, both Ca2+ entry via VDCC s and Ca2+ release from internal stores may contribute to the Ca2+ mobiliza tion; and under strong muscarinic stimulation, Ca2+ entry pathways resistan t to VDCC blockers may also contribute to it.