Effect of pH on myofilament Ca(2+)-sensitivity in alpha-toxin permeabilized guinea pig detrusor muscle.
OBJECTIVE
To ascertain if the inotropic effects of altered intracellular pH on detrusor smooth muscle could be explained by a change in Ca(2+)-sensitivity of the contractile proteins.


METHODS
Guinea pig detrusor smooth muscle was permeabilized with alpha-toxin and exposed to solutions mimicking the composition of the intracellular compartment and of varying [Ca2+]. Isometric tension was measured during exposure to solutions of varying [Ca2+] at pH 6.3, 7.1 and 7.5.


RESULTS
At pH 7.1 the pCa (-log10[Ca2+]) required for half-maximal activation (pCa50) was 6.00 +/- 0.07 at 22C. A Hill coefficient of unity suggested lack of cooperativity in myofilament Ca2+ activation. A decrease of pH from 7.1 to 6.3 had no significant effect on the pCa50 value or the maximum Ca2+ activated force. An increase to pH 7.5 decreased the pCa50 value by 0.65 +/- 0.20 units but left maximum force unaffected.


CONCLUSIONS
The reduced Ca2+ sensitivity of detrusor myofilaments at alkaline pH could partly explain the negative inotropic effect of intracellular alkalosis in intact muscle. The positive inotropic effect of intracellular acidosis cannot, however, be explained by alteration to myofilament Ca2+ sensitivity.
Wu
C
C
Department of Pharmacology, UMDS, London, United Kingdom.
Kentish
J C
JC
Fry
C H
CH
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010738:Type C Phospholipases / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
D010738:Type C Phospholipases; D002118:Calcium