MEMBRANE REPOLARIZATION STOPS CAFFEINE-INDUCED CA2-MUSCLE CELLS( RELEASE IN SKELETAL)

We have combined the patch-clamp technique with fura-2 measurements to investigate whether the Ca2+-induced Ca2+-release channel is under th e control of membrane potential in rat skeletal myoballs. We report th at Ca2+ release induced by 10 mM caffeine is turned off by membrane re polarization, a phenomenon that we term RISC (repolarization-induced s top of Ca2+ release). The RISC phenomenon is voltage- and time-depende nt. It is evident only when the release channels are first transferred into a functionally ''voltage-activated'' state through membrane depo larization. The results demonstrate that membrane repolarization activ ely closes the caffeine-activated release channels and suggest that th e ryanodine receptor is actually the physiological depolarization-indu ced Ca2+-release channel. Thus, our data provide compelling evidence f or a bidirectional voltage control (depolarization and repolarization) of the Ca2+-release channel in the sarcoplasmic reticulum by a voltag e sensor in the transverse tubule membrane.