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

Abstract

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