The effects of cellular hypoxia on contraction and extracellular ion accumulation in isolated human detrusor smooth muscle.

Abstract

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. 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. 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. 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.