The effect of D600 on potassium contractures of slow muscle fibres of Rana temporaria.

(1) The effect of 30 microM D600 on the amplitude and time course of isometric contractures was studied in single slow fibres of Rana temporaria. (2) D600 only slightly reduced the amplitude of contractures evoked with 30 or 95 mM K-Ringer's. Maintenance of tension was strongly impaired by D600 only during exposure to 95 mM K. The caffeine contracture was not affected. (3) Addition of 10 mM Ca2+ or other divalent cations to the medium strongly counteracted the effect of D600 on maintained tension. The order of efficiency was Ca2+ = Ni2+ greater than Co2+ greater than Mn2+ much greater than Mg2+. (4) During 2 min exposure to 95 mM K-Ringer's the slow fibres inactivated to a variable degree; recovery from inactivation in normal Ringer's proceeded with a half time of the order of 1 min, while in the presence of D600 recovery was prolonged 3.3 to 27 times. (5) It is concluded that the effect of D600 on the contractile behaviour of slow fibres from Rana temporaria is predominantly due to a prolongation of the inactivated state. It is suggested that D600 binds to a site at the outer membrane surface which also binds divalent cations and determines the degree of contractile inactivation during exposure to potassium. Blocking of Ca2+ channels is unlikely to be the mechanism of this D600-effect.