Studies of Shaker Mutations Affecting a K⁺ Channel in Drosophila

This chapter reviews the evidence that the Shaker locus in Drosophila is the site for the structural gene of a K⁺ channel. It discusses the strategies to be used for the molecular cloning of the Shaker locus. The recently isolated hybrid dysgenesis-induced Shaker mutants, which can be useful in the initial cloning and subsequent analysis of DNA from the Shaker locus, are described. The molecular studies of K⁺ channels are important because these channels play important roles in the control of neuronal activity and synaptic efficacy. The genetics of Drosophila and mutations of the Shaker locus offer an alternative approach for cloning K⁺ channels in the absence of high-affinity toxins or antibodies against K⁺ channels. In addition to providing a starting point for cloning, dysgenesis-induced Shaker mutants can also supply abundant new mutations that are considered useful in later molecular analysis. Genetic analyses using electrophysiological assays including voltage clamping provide strong evidence that the Shaker locus contains the structural gene for a K⁺ channel, the A channel.