EFFECT OF PH ON MYOFILAMENT CA2-SENSITIVITY IN ALPHA-TOXIN-PERMEABILIZED GUINEA-PIG DETRUSOR MUSCLE()

Purpose: To ascertain if the inotropic effects of altered intracellula r pH on detrusor smooth muscle could be explained by a change in Ca2+- sensitivity of the contractile proteins. Materials and Methods: Guinea pig detrusor smooth muscle was permeabilized with alpha-toxin and exp osed to solutions mimicking the composition of the intracellular compa rtment and of varying [Ca2+]. Isometric tension was measured during ex posure to solutions of varying [Ca2+] at pH 6.3, 7.1 and 7.5. Results: At pH 7.1 the pCa (-log(10)[Ca2+]) required for half-maximal activati on (pCa(50)) was 6.00 +/- 0.07 at 22C. A Hill coefficient of unity sug gested lack of cooperativity in myofilament Ca2+ activation. A decreas e of pH from 7.1 to 6.3 had no significant effect on the pCa(50) value or the maximum Ca2+ activated force. An increase to pH 7.5 decreased the pCa(50) value by 0.65 +/- 0.20 units but left maximum force unaffe cted. Conclusions: The reduced Ca2+ sensitivity of detrusor myofilamen ts at alkaline pH could partly explain the negative inotropic effect o f intracellular alkalosis in intact muscle. The positive inotropic eff ect of intracellular acidosis cannot, however, be explained by alterat ion to myofilament Ca2+ sensitivity.