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