D600 prolongs inactivation of the contractile system in frog twitch fibres

Abstract

(1) Single twitch fibres were dissected from tibialis muscles ofRana temporaria and used to study the effect of D600 (gallopamil) on potassium-induced contractures. (2) 95 mM K-Ringer's was applied for 8–15 s at intervals of generally 2.5–5 min; at temperatures of 6–8°C and in the absence of D600 the amplitude of the contractures remained fairly constant. After pretreatment with D600 (30 μM) a single (conditioning) K-contracture was sufficient to ‘paralyze’ the fibres (cf. Eisenberg et al. 1983). (3) Complete paralysis could also be achieved at 18–20°C. In three fibres a single conditioning K-application was sufficient; in two more fibres two or three conditioning K-applications were required. (4) D600-paralysis could not only be achieved with high K-concentrations but also by conditioning with subor suprathreshold K-concentrations (20–40 mM); the duration of the conditioning periods required to induce complete paralysis was approximately the same before and after D600-treatment. (5) Contractures were partially abolished by application of 20–40 mM K-Ringer's for short conditioning periods; after D600-treatment the degree of contracture loss was similar.

(6) At low temperature the state of partial or complete paralysis induced by subthreshold K-concentrations and D600 was maintained for long periods of time. (7) The presence of 10 mM Ca²⁺ did not protect the fibres from being paralyzed by treatment with D600 and high K-Ringer's at low temperature; however, more than one conditioning K-application was required. (8) Resting and action potentials of paralyzed fibres were not significantly different from control values. However, endplate potentials were reduced in size, and failure of neuromuscular transmission was observed in some of these fibres. (9) It is concluded that D600 prolongs the state of inactivation of the contractile mechanism, while the development of inactivation does not seem to be markedly affected.