Molecular Biology of High-Conductance, Ca2+-Activated Potassium Channels
The pore-forming α-subunit of the large-conductance, voltage- and Ca2+-activated K+ channel (BK, BKCa, or Slo1) was first cloned by utilizing the Drosophila Slowpoke (Slo) mutant (Atkinson et al., 1991), which carries homozygous mutant Slowpoke alleles. Flight muscles from this mutant fly lacked a Ca2+-activated K+ current (Elkins et al, 1986), whereas functional exprcssion of the Stowpoke wild-type cDNA (dSlol) yielded voltage- and Ca2+-activated K+ currents in Xenopus oocytes (Adelman et al, 1992). A large variety of dSlol isoforms are generated by alternative splicing, and some of them show large functional differences, including changcs in kinctics, singlc-channel conduc-tance, and Ca2+ and voltage sensitivities (Lagrutta et al, 1994). A series of vertebrate BKCa Channel ±-subunit clones including human hSlol (Butler et al, 1993; Dworetzky et al, 1994; Pallanck and Ganetzky, 1994; Tseng-Crank et al, 1994; McCobb et al, 1995; Wallner et al, 1995; Vogalis et al, 1996; Jiang et al, 1997; Morita et al, 1997; Jones et al, 1998) were isolated by homology Screening, and an ortholog in Caenorhab-ditis. elegans, nSlol (Wei et al, 1996), has been identified (Fig. 1A). The deduced protein of these cDNA clones shows similarities to other Kv Channels in the voltage sensor and in the “pore” region, which determines ionic conductance and selectivity (Figs. 1B, 1C, and 2A).
KeywordsCodon Cysteine Carboxyl Arginine Trypsin
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