Source of activator calcium in isolated guinea pig and human gastric muscle cells.
The source of Ca2+ responsible for contraction was examined in suspensions of smooth muscle cells and in perfused single muscle cells from guinea pig and human stomach. In both preparations removal of Ca2+ from the medium or addition of the Ca2+ channel blocker methoxyverapamil had no effect on the contractile response to various agonists, including cholecystokinin octapeptide (CCK-8) and acetylcholine, but inhibited the response to high extracellular K+ by 76-82%. Repeated stimulation of guinea pig or human single muscle cells in Ca2+-free medium, or in the presence of methoxyverapamil caused a progressive decrease and eventual abolition of contractile response; response was restored on restitution of Ca2+ to the medium or elimination of methoxyverapamil. Measurement of 45Ca2+ content in guinea pig muscle cells showed that CCK-8 had no effect on the rate of Ca2+ influx but increased the rate of Ca2+ efflux transiently by sixfold. Net peak efflux coincided with the time of peak contraction and was stoichiometrically related to the degree of contraction. Equipotent, maximally effective contractile doses of CCK-8, acetylcholine, and methionine-enkephalin caused equivalent degrees of net Ca2+ efflux. The results indicate that contractile agonists cause release of Ca2+ from a depletable intracellular store in gastric muscle cells. The release is accompanied by a dose-dependent increase in Ca2+ efflux and is capable of sustaining an initial maximal contraction. Repeated contractile activity requires influx of Ca2+ from extracellular sources.
K N
KN
Bitar
G M
GM
Burgess
J W
JW
Putney
G M
GM
Makhlouf
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media; D004744:Enkephalin, Methionine / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology* / Q000378:metabolism; D011189:Potassium Chloride / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology; D013270:Stomach / Q000166:cytology*
D002121:Calcium Channel Blockers; D003470:Culture Media; D007473:Ion Channels; D005711:Gallopamil; D004744:Enkephalin, Methionine; D011189:Potassium Chloride; D012844:Sincalide; D000109:Acetylcholine; D002118:Calcium