The effect of metabolic inhibition on rat uterine intracellular pH and its role in contractile failure.

Although intracellular pH (pHi) is expected to change during inhibition of oxidative phosphorylation and to affect force, there have been no simultaneous measurements of its effect on pHi and force in smooth muscle. Therefore, we have investigated the relationship between force and pHi in strips of longitudinal rat myometrium, loaded with the pH-sensitive indicator carboxy-SNARF and simultaneously measured tension. The application of cyanide produced an abolition of spontaneous contractions and a rapid initial fall in pHi. In 9/19 preparations pHi then started to return to resting values but there was no corresponding restoration of force. Cyanide and weak base were simultaneously added to uterine preparations to prevent any acidification; force still fell. Addition of cyanide to depolarized preparations also produced an acidification and a fall in force. Depolarization of preparations in which spontaneous force had been abolished by cyanide often produced a transient rise in force, despite further acidification of the cytoplasm. Cyanide produced an acidification in zero Ca(2+)-containing solution, similar to that in the presence of Ca2+ indicating little role for changes in [Ca2+] in producing the acidification. It is concluded that cyanide decreases pHi and force in the uterus, but that there is not a simple relationship between the two.