Stimulus-dependent modulation of smooth muscle intracellular calcium and force by altered intracellular pH

Abstract

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.

Modulation of force induced by pH in the guinea-pig uterus examined at two stages of the oestrous cycle

“…Intracellular acidification, at constant pHo, abolished spontaneous contractions in all tissues tested. These effects was similar to those reported in rats and women (Taggart and Wray, 1993, Parratt et al, 1994, 1995a (Taggart et al, 1996). Thus, acidification reduced [Ca2+].…”

“…modulate force in a variety of smooth muscles (Wray, 1988;Austin and Wray, 1994;Burdyga et al, 1996). In myometrial smooth muscle obtained from both rats (Taggart and Wray, 1993) and women (Parratt et al, 1994(Parratt et al, , 1995a, intracellular acidification decreases, and intracellular alkalinization increases, spontaneous force.…”

“…In myometrial smooth muscle obtained from both rats (Taggart and Wray, 1993) and women (Parratt et al, 1994(Parratt et al, , 1995a, intracellular acidification decreases, and intracellular alkalinization increases, spontaneous force. Extracellular pH (pHo) change also affects force in myometrium but its effects vary with gestational state (Naderali and Wray, 1996;Taggart et al, 1997). In the human uterus, pH increases throughout gestation (Parratt et al, 1995b); an effect that has been attributed to hormonal changes.…”

The Physiological Basis of Uterine Contractility: A Short Review

“…In particular pH has been shown to be a potent modulator of uterine force, with intracellular acidification reducing or even abolishing contractions (Taggart & Wray, 1993;Parratt et al 1994). We have previously found that when intracellular pH is lowered, Ca 2+ transients are suppressed and intracellular Ca 2 falls (Taggart et al 1996). Measurement of membrane potential showed action potentials were also abolished by acidification (Taggart et al 1996).…”

Lactate Level in Amniotic Fluid, a New Diagnostic Tool

“…One important finding, which has influenced the hypotheses for this thesis, is that the myometrium is a lactate producer (Taggart & Wray 1993;Taggart et al 1996;Taggart et al 1997;Taggart & Wray 1998;Wray et al 2003;Quenby et al 2004), and the level will increase when there is a lack of oxygen.…”