FUNCTIONAL DIFFERENCES AMONG ALTERNATIVELY SPLICED VARIANTS OF SLOWPOKE, A DROSOPHILA CALCIUM-ACTIVATED POTASSIUM CHANNEL

The Slowpoke locus of Drosophila melanogaster encodes a family of alte rnatively spliced mRNAs which encode large conductance calcium-activat ed potassium channels. Variability resides in blocks of amino acids de signated boxes A, C, E, G, and I. Oocytes were injected with cRNAs tha t had been chosen for direct functional comparison of single box diffe rences. Single channel records from inside-out patches of oocyte membr anes expressing A1 or A3 forms, E1 or E2 forms, and G2-G5 forms were a nalyzed and compared. The main functional difference between A1 and A3 was in unitary conductance, whereas the main difference in properties between E1 and E2 was in calcium sensitivity. Activation kinetics wer e different between G3 and G5, but not consistently in different A and E box backgrounds. The results indicate that alternative splicing of a common RNA precursor contributes to the functional diversity of the expressed channel. Our findings suggest that the variable region of th e Slowpoke channel subunit comprises modular, yet interactive function al domains which influence the essential features of unit conductance, calcium sensitivity, and gating.