WANDERLUST KINETICS AND VARIABLE CA2-SENSITIVITY OF DSLO, A LARGE-CONDUCTANCE CA2+-ACTIVATED K+ CHANNEL, EXPRESSED IN OOCYTES (VOL 70, PG 2640, 1996)()

Cloned large conductance Ca2+-activated K+ channels (BK or maxi-K+ cha nnels) from Drosophila (dSlo) were expressed in Xenopus oocytes and st udied in excised membrane patches with the patch-clamp technique. Both a natural variant and a mutant that eliminated a putative cyclic AMP- dependent protein kinase phosphorylation site exhibited large, stow fl uctuations in open probability with time. These fluctuations, termed ' 'wanderlust kinetics,'' occurred with a lime course of tens of seconds to minutes and had kinetic properties inconsistent with simple gating models. Wanderlust kinetics was still observed in the presence of 5 m M caffeine or 50 nM thapsigargin, or when the Ca2+ buffering capacity of the solution was increased by the addition of 5 mM HEDTA, suggestin g that the wanderlust kinetics did not arise from Ca2+ release from ca ffeine and thapsigargin sensitive internal stores in the excised patch . The slow changes in kinetics associated with wanderlust kinetics cou ld be generated with a discrete-state Markov model with transitions am ong three or more kinetic modes with different levels of open probabil ity. To average out the wanderlust kinetics, large amounts of data wer e analyzed and demonstrated up to a threefold difference in the [Ca2+] (i) required for an open probability of 0.5 among channels expressed f rom the same injected mRNA. These findings indicate that cloned dSlo c hannels in excised patches from Xenopus oocytes can exhibit large vari ability in gating properties, both within a single channel and among c hannels.