COOPERATIVE SUBUNIT INTERACTIONS IN C-TYPE INACTIVATION OF K CHANNELS

C-type inactivation of potassium channels is distinct from N-terminal mediated (N-type) inactivation and involves a closing of the outer mou th of the channel. We have investigated the role of the individual sub units of the tetrameric channel in the C-type inactivation conformatio nal change by comparing the inactivation rates of channels constructed from different combinations of subunits, The relationship between the inactivation rate and the number of fast subunits is exponential, as would be predicted by a cooperative mechanism where the C-type conform ational change involves all four subunits, and rules out a mechanism w here a conformational change in any of the individual subunits is suff icient for inactivation. Subunit interactions in C-type inactivation a re further supported by an interaction between separate mutations affe cting C-type inactivation when in either the same or separate subunits .