The effects of metabolic inhibition on force, Ca2+ and pHi in guinea-pig ureteric smooth muscle

The effect of metabolic inhibition on the contractile function of adult guinea-pig ureter has been investigated. Strips of ureteric smooth muscle were loaded with Indo-1 or SNARF to measure intracellular [Ca2+] ([Ca2+]i) or pH (pHi) simultaneously with force. Inhibiting oxidative phosphorylation with cyanide rapidly reduced phasic contractions and the associated Ca2+ transients, after initial transient increases. The effects of cyanide were reversible and related to the amount of contractile activity undertaken. Inhibition of glycolysis with iodoacetate abolished all force. In high-K+-depolarised preparations, cyanide reduced the tonic contraction, but this was not accompanied by a reduction in [Ca2+]i, suggesting a desensitisation of the myofilaments. Cyanide produced a fall in pHi, which may underlie the initial transient increase in force. These data suggest that metabolic inhibition reduces force in the ureter by affecting both excitation and hence the Ca2+ transient, and at the myofilaments to reduce their sensitivity to Ca2+. Thus when oxidative metabolism is impaired contractile dysfunction may arise in the ureter.