DSLO INTERACTING PROTEIN-1, A NOVEL PROTEIN THAT INTERACTS WITH LARGE-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS

Large-conductance calcium-activated potassium channels (BK channels) a re activated by depolarized membrane potential and elevated levels of intracellular calcium. BK channel activity underlies the fast afterhyp erpolarization that follows an action potential and attenuates neurotr ansmitter and hormone secretion, Using a modified two-hybrid approach, the interaction trap, we have identified a novel protein from Drosoph ila, dSLIP1 (dSLo interacting protein), which specifically interacts w ith Drosophila and human BK channels and has partial homology to the P DZ domain of alpha 1 syntrophin, The dSLIP1 and dSlo mRNAs are express ed coincidently throughout the Drosophila nervous system, the two prot eins interact in vitro, and-they may be coimmunoprecipitated from tran sfected cells. Coexpression of dSLIP1 with dSlo or hSlo BK channels in Xenopus oocytes results in reduced currents as compared with expressi on of BK channels alone; current amplitudes may be rescued by coexpres sion with the channel domain that interacts with dSLIP1. Single-channe l recordings and immunostaining of transfected tissue culture cells su ggest that dSLIP1 selectively reduces Slo BK currents by reducing the number of BK channels in the plasma membrane.