Several different methods have been employed in the study of voltage-gated ionchannels. Electrophysiological studies on excitable cells in vertebrates and molluscs haveshown that many different voltage-gated potassium (K+) channels and sodium channelsmay coexist in the same organism. Parallel genetic studies in Drosophila have identifiedmutations in several genes that alter the properties of specific subsets of physiologicallyidentified ion channels. Chapter 2 describes molecular studies that identify two Drosophilahomologs of vertebrate sodium-channel genes. Mutations in one of these Drosophilasodium-channel genes are shown to be responsible for the temperature-dependent paralysisof a behavioural mutant parats. Evolutionary arguments, based on the partial sequences ofthe two Drosophila genes, suggest that subfamilies of voltage-gated sodium channels invertebrates remain to be identified.
In Drosophila, diverse voltage-gated K+ channels arise from alternatively splicedmRNAs generated at the Shaker locus. Chapter 3 and the Appendices describe the isolationand characterization of several human K+-channel genes, similar in sequence to Shaker.Each of these human genes has a highly conserved homolog in rodents; thus, this K+-channelgene family probably diversified prior to the mammalian radiation. Functional K+channels encoded by these genes have been expressed in Xenopus oocytes and theirproperties have been analyzed by electrophysiological methods. These studies demonstratethat both transient and noninactivating voltage-gated K+ channels may be encoded bymammalian genes closely related to Shaker. In addition, results presented in Appendix 3clearly demonstrate that independent gene products from two K+-channel genes mayefficiently co-assemble into heterooligomeric K+ channels with properties distinct fromeither homomultimeric channel. This finding suggests yet another molecular mechanism forthe generation of K+-channel diversity.
