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 microM produced an oscillatory or sustained type of depolarization and at 100 microM, the latter type depolarization. Depletion of internal Ca2+ stores blocked the oscillatory response, but not the sustained responses to 2 microM and 100 microM CCh, although their decay after reaching the peak became faster. Blocking voltage-dependent Ca2+ channels (VDCCs) blocked both types of response to 2 microM CCh, but only slowed the initial rising phase of 100 microM CCh responses. Combination of Ca2+ store depletion and VDCC blockade abolished the responses to 2 microM CCh again and decreased those to 100 microM CCh in peak amplitude and persistency. Combination of Ca2+ store depletion with removal of extracellular Ca2+ markedly reduced or abolished the 100 microM 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.
Unno
T
T
Department of Veterinary Medicine, Faculty of Agriculture, United Graduate School, Gifu University, Japan.
Inaba
T
T
Ohashi
H
H
Takewaki
T
T
Komori
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009529:Nicardipine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018679:Cholinergic Agonists; D004791:Enzyme Inhibitors; D011976:Receptors, Muscarinic; D019284:Thapsigargin; D002217:Carbachol; D009529:Nicardipine; D002118:Calcium