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⁺- dependent, voltage-dependent BK-type channels are found in rat chromaffin cells and are largely segregated into different cells. Here we test the hypothesis that, within the population of cells that express inactivating BK current (BK(i) current), the BK, channels are largely heteromultimers composed of inactivation-competent subunits (bk(i))and noninactivating subunits (bk(s)). Several independent types of evidence support this view. The gradual removal of inactivation by trypsin is consistent with the idea that in most cells and patches there are, on average, about two to three inactivation domains per channel. In addition, several aspects of blockade of BK(i) current by charybdotoxin (CTX) are consistent with the idea that BK(i) channels contain differing numbers (one to four) of relatively CTX-resistant bk(i) subunits. Finally, the frequency of occurrence of noninactivating BK(s) channels in patches with predominantly noninactivating BK(i) channels is consistent with the binomial expectations of random, independent assembly of two distinct subunite, if most cells have, on average, about two to three bk(i) subunits per channel. These results suggest that the phenotypic properties of BK(i) currents and the resulting cellular electrical excitability may exhibit a continuum of behavior that arises simply from the differential expression of two distinct subunits.