[
International Worm Meeting,
2011]
Small conductance calcium-activated potassium (SK) channels function to regulate neuronal firing frequency through the generation of a component of the medium afterhyperpolarization that follows action potentials. In humans, irregular action potential frequency underlies diseases such as ataxia, epilepsy, schizophrenia and Parkinson's disease. An SK channel homologue, kcnl2, is encoded for by the F08A10.1 gene in C. elegans. Kcnl2 shares 38% and 34% homology with the human SK2 and SK3 channels, respectively, and shows a great degree of conservation in the six transmembrane domains, the pore motif and the calmodulin binding domain. These structural motifs have been shown to be important for the channel's biogenesis and pharmacology in humans and mice. The F08A10.1 gene was amplified from the WRM063DE08 fosmid and was fused to GFP at the two proposed stop codons. Microinjection of these DNAs indiscriminately yields overexpression of all splice variants. Transgenic lines show that the kcnl2 channel was localized to neurons of the head, the ventral nerve cord, the dorsal cord and the phasmids of the tail. Phenotypic analyses of both knockout and overexpressing transgenic lines identify a potential role of kcnl2 in development and egg laying. We propose that C. elegans will serve as an elegant and simplistic neurological model to study the physiological functions of SK channels that are otherwise masked in complex mammalian systems.