CDRK AND DRK1 K+ CHANNELS HAVE CONTRASTING LOCALIZATIONS IN SENSORY SYSTEMS

Molecular cloning of mammalian potassium channels has revealed an extensively heterogeneous superfamily of potassium channels derived from four basic subfamilies, Shaker, Shaw, Shal and Shab, each with multiple members.3-5,10,13,18,19,22,23,25,26,29,31,33 The families were first identified in Drosophila, in which subfamily heterogeneity is derived by alternative splicing, while in mammals mainly distinct genes give rise to channel subtypes. Further diversity of mammalian potassium channels is demonstrated by the identification of some which do not belong to any of the four main subfamilies.9,30 Although potassium channels are differentiated into fast-inactivating and delayed rectifier types, differential functions of the many mammalian potassium channels are unclear. Moreover, potassium channels function as homotetramers, though in principle heterotetramers might have a physiological role as is the case with heteromers of neurotransmitter receptor subunits.6 Insight into differential functions of potassium channels may be provided by their regional and subcellular localizations. In the rat brain in situ hybridization and immunohistochemistry have revealed distinct regional localizations for various subfamilies.3,9,12,13,28,32 In one instance a particular subfamily predominated in cell bodies and another in axons.28 We demonstrated dramatically different localizations for two members of the Shab subfamily, circumvallate papilla delayed rectifier K+ channel (CDRK) and delayed rectifier potassium channel 1 (DRK1), which in major portions of their sequences display more than 90% amino acid identity.'' In a number of brain regions they occur in distinct neuronal cell types or subcellular compartments, with CDRK predominantly localized diffusely over soma and in fibers and DRK1 most evident in soma and dendritic process.