The effects of fructose 1,6-diphosphate, caffeine and dantrolene sodium on suxamethonium-induced contractures in denervated rat skeletal muscle.

Abstract

Previously unidentified forms of suxamethonium-induced contractures have been investigated in chronically denervated rat extensor digitorum longus (EDL) muscle at 20 degrees C. Contractures were assigned to groups 1-6 on the basis of the peak tension (Tp1) during 0-10 min exposure to the drug (3.0 x 10(-5) M), (7.0 x 10(-6) M), and (3.5 x 10(-6) M) and the subsequent retention, increase, or decrease in tension (Tp2), during the further 10 min. It is proposed that four stages exist in the development of contractile changes at 1-7, 8-35, 36-70 and 70-130 days after denervation (DPD) and that contractility is lost at 147 days after denervation. Initial changes, although present in EDL muscles in group 1 at 2.0 DPD s.d. +/- 1 (n = 7) in response to the drug (3.0 x 10(-5) M), were more apparent in EDL muscles in group 2 which were identified at 5.5 DPD s.d. +/- 1.6 (n = 7) by an excessive contracture response (Tp2) to the drug (3.0 x 10(-5) M), 18.3 mN s.d. +/- 10.6. At 5.0 DPD s.d. +/- 2.7 (n = 5) contracture tension (Tp2) was commensurate with membrane depolarization, 13.1 mN/33.1 mV, but residual tension increased to 23.3 mN during the Krebs wash (80 min) whilst membrane depolarization decreased to 9.2 mV. Also, at 4.3 DPD s.d. +/- 2.3 (n = 5) tension (Tp2) increased significantly (P less than or equal to 0.05) in the presence of caffeine (4.1 x 10(-3) M).(ABSTRACT TRUNCATED AT 250 WORDS)