The Effects of Cellular Hypoxia on Contraction and Extracellular Ion Accumulation in Isolated Human Detrusor Smooth Muscle

PURPOSE: The effect of cellular hypoxia on the phasic isometric contraction of isolated preparations of human detrusor muscle was measured and the influence of the accumulation of extracellular H+ and K+ on the inotropic effects ascertained. MATERIAL AND METHODS: Strips of human detrusor smooth muscle were field stimulated and superfused with an HCO3-/CO2 medium. Cellular hypoxia was generated by superfusion with 1) a low PO2 (approximately 5 kPa) solution; 2) 5 mM. Na azide; or 3) 10 mM. 2-deoxyglucose and omission of glucose and Na pyruvate. Extracellular pH or [K+] was simultaneously measured with ion-selective microelectrodes placed in the muscle strip. RESULTS: Interventions produced a reversible contractile decay in the steady state, but the decay was preceded by a transient increase of force in most preparations. A small rise of the extracellular [K+] was also measured, but the effect was significantly smaller with 2-deoxyglucose. Extracellular acidosis was recorded with low PO2 and Na azide, but was absent with 2-deoxyglucose. The extracellular acidosis was usually preceded by a transient extracellular alkalosis. CONCLUSION: Part of the contractile changes under these conditions could result from an extracellular acidosis generated via glycolysis; the accumulation of extracellular K+ was insufficient to exert inotropic effects.