Comparison of the effects of mefloquine and ryanodine on the directly stimulated rat hemidiaphragm preparation

Abstract

The effects of the antimalarial agent mefloquine on directly stimulated rat hemidiaphragm were investigated after nerve transmission had been blocked with α-bungarotoxin. Mefloquine (50 and 75 μM) caused contractures and diminished directly stimulated twitch responses. The mefloquine-induced contracture was significantly diminished in low Ca2+ Krebs-Henseleit solution and after pretreatment with phospholipase C. It was potentiated following an initial exposure to ryanodine. Mefloquine, as well as ryanodine, reduced the caffeine contractures obtained in low Ca2+ media. The results suggest that Ca2+-induced Ca2+ release, involving the action of mefloquine on some phospholipid component of the sarcolemma, appears to be important in the initiation of the contracture. The loss in caffeine response following pretreatment with mefloquine indicates that mefloquine also causes depletion of Ca2+ from sarcoplasmic reticulum stores.