Shaker gene

Historically the Shaker (Sh) K channel was the first K channel which was cloned and characterized [6-10]. Subsequently many more channel cDNAs and genes have been isolated and studied. Yet Sh channels remained in the forefront of channel research. The study of Sh channel mutants has provided the most thorough insight into structure-function relationships of K channels to date. I will first discuss in this chapter the primary sequences of voltage-gated channels. I will only use a few selected examples for discussion. As of this time, so many related K channel protein sequences have been published that it is not feasible to discuss all of them. Subsequently, I will describe in detail the present knowledge about functional K" " channel domains which are implicated in activation, inactivation and selectivity of the channel. 

Fig. 4. Schematic organization of the Shaker K channel gene. The coordinates of the physical map are as in [9]. The direction of transcription is indicated by arrows. Approximate location of exons is given by boxes. Open box corresponds to noncoding exons, lettered boxes to alternative amino-terminal ends of Shaker channel proteins and the core region, respectively, numbered boxes to the two alternative carboxy-terminal ends. Exon numbers are as in [53].

Two other myosin types have been implicated in hearing and vestibular function [62]. The defect in the Snell s waltzer mouse was found to be a mutation in a myosin VI gene that produces degeneration of the cochlea and vestibular apparatus. Myosin VI is localized to the cuticular plate of the hair cell under stereocilia. Similarly, mutations in a myosin VII gene are responsible for the shaker-1 mouse and several human genetic deafness disorders. This myosin, myosin Vila, is found in a band near the base of the stereocilia distinct from distributions of myosin ip and myosin VI. 

Galeotti, N., Ghelardini, C., Papucci, L., Capaccioli, S., Quattrone, Bartolini, A. An antisense oligonucleotide on the mouse Shaker-like potassium channel Kv1.1 gene prevents antinociception induced by morphine and baclofen, The Journal of Pharmacology and Experimental Therapeutics 1997a, 281, 941-949. 

Kim, E., Day, T.A., Bennett, J.L. and Pax, R.A. (1 995a) Cloning and functional expression of a Shaker-related voltage-gated potassium channel gene from Schistosoma mansoni (Trematoda Digenea). Parasitology 110, 1 71-180. 

The first voltage-gated potassium channel to be identified was the gene encoding the Shaker mutation in the fruit fly Drosophila. Figure 9.3 presents the hrst pictures of the tetrameric Shaker K+ channel with... 

Figure 30-18 (A) K+ currents recorded from Xenopus laevus oocytes carrying cloned genes of Drosophila shaker K+ channels under two-electrode voltage-clamp conditions. Trace 1.4-IR was obtained from a cell expressing channels that lack the inactivation gate. Trace 1.4-IR + Pj2/ obtained from a cell expressing P subunits as well, shows rapid self-inactivation. (From Zhou et (B) Composite model of a voltage-dependent K+ charmel. The pore structure in the a subunit is represented by the...

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