PROCAINE EFFECTS ON SINGLE SARCOPLASMIC-RETICULUM CA-2(+) RELEASE CHANNELS

The effects of the Ca2+-induced Ca2+ release blocker procaine on indiv idual sarcoplasmic reticulum Ca2+ release channels have been examined in planar lipid bilayers. Procaine did not reduce the single channel c onductance nor appreciably shorten the mean open times of the channel; rather, it increased the longest closed time. These results indicated that procaine interacted selectively with a closed state of the chann el rather than with an open state. Gating of the sarcoplasmic reticulu m Ca2+ release channel was described by a modified scheme of Ashley an d Williams (1990. J. Gen. Physiol. 95:981 1005), including an addition al long-lived closed state. Computer simulations determined that proca ine was more likely to interact with this long-lived Ca2+-bound closed state of the channel rather than with other states of the channel. Si mulations with the same model were also able to reproduce a prominent Ca2+-sensitive transition between ''random'' and ''bursting'' forms of gating of the channel, variations of which may account for ''gearshif t'' behavior reported in studies with this and other single channels.