Analysis of multiple conductance states observed in Ca2+ release channel of sarcoplasmic reticulum.

Both slowly and rapidly fluctuating currents were observed after incorporating a heavy sarcoplasmic reticulum (HSR) vesicle or a purified ryanodine receptor (RyR) of rabbit skeletal muscle into a lipid bilayer. The responses to the cis side Ca2+, ruthenium red and ryanodine confirmed that both were the currents through one Ca2+ release channel. From the analysis of conductance states, RyR is supposed to have two different configurations. The current through one configuration has a high reversal potential (HRP) (-18 mV) and that through another one has a low reversal potential (LRP) (-11 mV). The current with HRP fluctuates rapidly but the current with LRP always fluctuates slowly. From the analysis of both rapidly and slowly fluctuating currents, it was shown that there are four pores in RyR. Among the conductance states of the slowly fluctuating current with LRP, the conductance of the 4OP (four opened pores) state was smaller than four times that of 1OP (one opened pore). To explain this fact, we proposed a model of the channel, a large central pore in series with four small parallel pores. The calculation according to the model has a good fit with the bilayer measurement.