Uterine activity in labour can produce acidosis. In turn, intracellular pH change can greatly alter the spontaneous contractile ability of human myometrium, although the mechanisms involved are poorly understood. We have therefore determined the effects of both intra- and extracellular pH change on contractile activity and intracellular [Ca²⁺] during spontaneous, oxytocin-induced and high K⁺ depolarization-induced stimulation of longitudinal strips from human myometrium.

Human non-labouring myometrial tissue was obtained with ethical permission and informed consent, from women undergoing elective Caesarean section at term (37Ð42 weeks gestation). Strips of longitudinal muscle were incubated overnight with 7 mM indo-1 AM for [Ca²⁺]_i measurements. These were then attached to a force transducer and tissue superfused continuously with physiological saline at 35Ð37 °C. Changes in pH_i were produced by isosmotic replacement (40 mM) of NaCl with sodium butyrate or NH₄Cl. Changes in pH_o were produced by addition of NaOH or HCl. Oxytocin (10 nM) and high-K⁺ at 40 mM were used. EGTA (1 mM) was added to solutions of zero calcium. Statistical analysis was performed on paired data using Student’s t test (95 % confidence); n is the number of samples.

Our data show that both intracellular and extracellular acidification significantly reduce or even abolish phasic activity whether arising spontaneously or in the presence of oxytocin (n = 7). Furthermore, these contractile changes can be accounted for by the changes in [Ca²⁺]. Alkalinization produced the opposite effects, i.e. phasic contractions and Ca²⁺ transients increased (n = 7). However, baseline or maintained tension changes could not be accounted for by changes in [Ca²⁺]_i. Thus intracellular acidification reduced baseline tension in both spontaneous and oxytocin-stimulated preparations and reduced maintained tension in depolarised preparations, but increased [Ca²⁺]_i in all cases. Application of weak acid, in calcium-free solution, both with (n = 4) and without oxytocin (n = 7) led to a rise in [Ca²⁺]_i but an immediate loss of tension in all cases.

We suggest that the effects on phasic activity are due to inhibition of Ca²⁺ entry via surface membrane channels and during periods of maintained tension (as produced with application of high-K⁺ solution) pH-sensitive Ca²⁺ release from the SR occurs but is not sufficient to overcome the inhibitory effects at the myofilaments. We conclude that alterations of both intra- and extracellular pH significantly affect Ca²⁺ signalling and force production in the human myometrium and may therefore contribute to dysfunction in labour.

We are grateful to The Wellcome Trust for providing a fellowship to S.J. Pierce, the Royal Thai Government for supporting S. Kupittayanant and to the patients and staff of the Liverpool Women’s Hospital.

All procedures accord with current local guidelines.