Stimulus-dependent modulation of smooth muscle intracellular calcium and force by altered intracellular pH.
Measurements of simultaneous force and intracellular Ca2+ concentration ([Ca2+]i) in rat uterine smooth muscle have been made to elucidate the mechanisms involved when force produced spontaneously, by high-K+ depolarization or carbachol is altered by a change of intracellular pH (pHi). Rises in force and [Ca2+]i were closely correlated for all forms of contraction, with the Ca2+ transient peaking before force. In spontaneously active preparations, alkalinization significantly increased, and acidification decreased, force and [Ca2+]i. Inhibition of the sarcoplasmic reticulum ATPase (cyclopiazonic acid) did not affect these changes, whereas removal of external Ca2+ abolished both responses, suggesting that the effect of pHi is on Ca2+ entry. Alkalinization caused a prolongation of the action potential complex, associated with a potentiation of contractile activity. Acidification produced hyperpolarization and abolition of action potentials and spontaneous activity, but did not prevent brief applications of carbachol or high-K+ from producing depolarization and increasing force, suggesting no impairment of the mechanism of generation of the action potential. For depolarized preparations, acidification increased tonic force and [Ca2+]i; the increase in the calcium signal persisted in zero-external calcium. In the presence of carbachol, acidification transiently increased force and [Ca2+]i, followed by a reduction in both. It is concluded that changes in pHi act at more than one step in excitation-contraction coupling and that changes in [Ca2+]i can account for most of the changes in uterine force.
Taggart
M J
MJ
Physiological Laboratory, Crown Street, The University of Liverpool, PO Box 147, Liverpool L69 3BX, UK.
Burdyga
T
T
Heaton
R
R
Wray
S
S
D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects
D002087:Butyrates; D020148:Butyric Acid; D002217:Carbachol; D011188:Potassium; D002118:Calcium