STIMULUS-DEPENDENT MODULATION OF SMOOTH-MUSCLE INTRACELLULAR CALCIUM AND FORCE BY ALTERED INTRACELLULAR PH

Measurements of simultaneous force and intracellular Ca2+ concentratio n ([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 p H (pH(i)). Rises in force and [Ca2+](i) were closely correlated for al l forms of contraction, with the Ca2+ transient peaking before force. In spontaneously active preparations, alkalinization significantly inc reased, and acidification decreased, force and [Ca2+](i). Inhibition o f the sarcoplasmic reticulum ATPase (cyclopiazonic acid) did not affec t these changes, whereas removal of external Ca2+ abolished both respo nses, suggesting that the effect of pH(i) is on Ca2+ entry. Alkaliniza tion caused a prolongation of the action potential complex, associated with a potentiation of contractile activity. Acidification produced h yperpolarization and abolition of action potentials and spontaneous ac tivity, but did not prevent brief applications of carbachol or high-K from producing depolarization and increasing force, suggesting no imp airment of the mechanism of generation of the action potential. For de polarized preparations, acidification increased tonic force and [Ca2+] (i); the increase in the calcium signal persisted in zero-external cal cium. In the presence of carbachol, acidification transiently increase d force and [Ca2+](i), followed by a reduction in both. It is conclude d that changes in pH(i) act at more than one step in excitation-contra ction coupling and that changes in [Ca2+](i) can account for most of t he changes in uterine force.