INACTIVATING BK CHANNELS IN RAT CHROMAFFIN CELLS MAY ARISE FROM HETEROMULTIMERIC ASSEMBLY OF DISTINCT INACTIVATION-COMPETENT AND NONINACTIVATING SUBUNITS

Inactivating and noninactivating variants of large-conductance, Ca2+-d ependent, voltage-dependent BK-type channels are found in rat chromaff in cells and are largely segregated into different cells. Here we test the hypothesis that, within the population of cells that express inac tivating BK current (BK, current), the BKi channels are largely hetero multimers composed of inactivation-competent subunits (bk(i)) and noni nactivating subunits (bk(s)). Several independent types of evidence su pport this view. The gradual removal of inactivation by trypsin is con sistent with the idea that in most cells and patches there are, on ave rage, about two to three inactivation domains per channel. In addition , several aspects of blockade of BK, current by charybdotoxin (CTX) ar e consistent with the idea that BKi channels contain differing numbers tone to four) of relatively CTX-resistant bk(i) subunits. Finally, th e frequency of occurrence of noninactivating BKs channels in patches w ith predominantly inactivating BKi channels is consistent with the bin omial expectations of random, independent assembly of two distinct sub units, if most cells have, on average, about two to three bk(i) subuni ts per channel. These results suggest that the phenotypic properties o f BKi currents and the resulting cellular electrical excitability may exhibit a continuum of behavior that arises simply from the differenti al expression of two distinct subunits.