<i>mSlo</i>
            , a Complex Mouse Gene Encoding "Maxi" Calcium-Activated Potassium Channels

Butler, Alice; Tsunoda, Susan; McCobb, David P.; Wei, Aguan; Salkoff, Lawrence

doi:10.1126/science.7687074

Cited by 629 publications

(563 citation statements)

References 30 publications

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“…2). The reason why this is unconventional is that Slo channels are defined based on their gating properties, for example Slo3 is pH-gated, Slo2 is Na + -gated and Slo1 is gated by Ca 2+ [26,[146][147][148]. Furthermore, the crystal structure of human Slo3 indicated the channel lacks a calcium-sensitive bowl [142].…”

Section: Potassium Channels Of Spermmentioning

confidence: 99%

Flagellar ion channels of sperm: similarities and differences between species

et al. 2015

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a b s t r a c tMotility and fertilization potential of mammalian sperm are regulated by ion homeostasis which in turn is under tight control of ion channels and transporters. Sperm intracellular pH, membrane voltage and calcium concentration ([Ca 2+ ] i ) are all important for sperm activity within the female reproductive tract. While all mammalian sperm are united in their goal to find and fertilize an egg, the molecular mechanisms they utilize for this purpose are diverse and differ between species especially on the level of ion channels. Recent direct recording from sperm cells of different species indicate the differences between rodent, non-human primate, ruminant, and human sperm on the basic levels of their ion channel regulation. In this review we summarize the current knowledge about ion channel diversity of the animal kingdom and concentrate our attention on flagellar ion channels of mammalian sperm.

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Section: Potassium Channels Of Spermmentioning

confidence: 99%

Flagellar ion channels of sperm: similarities and differences between species

et al. 2015

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“…Multiple splice variants are generated by alternative splicing and post-transcriptional mechanisms (Salkoff et al, 2006). The primary sequence of C. elegans SLO-1 has greater than 50% amino acid identity with the mammalian channels (Butler et al, 1993;McCobb et al, 1995;Salkoff et al, 2006) and 66% identity with Drosophila melanogaster (Adelman et al, 1992). To identify and categorize mammalian orthologs of SLO-1a (NP_001024259), and specifically to test the relationship with KCNMA1 (NP_002238), we constructed a molecular phylogeny (see Supplemental Information S2 for details).…”

Section: Methodsmentioning

confidence: 99%

Selective Toxicity of the Anthelmintic Emodepside Revealed by Heterologous Expression of Human KCNMA1 inCaenorhabditis elegans

Crisford¹,

Murray²,

O’Connor³

et al. 2011

Mol Pharmacol

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Emodepside is a resistance-breaking anthelmintic of a new chemical class, the cyclooctadepsipeptides. A major determinant of its anthelmintic effect is the calcium-activated potassium channel SLO-1. SLO-1 belongs to a family of channels that are highly conserved across the animal phyla and regulate neurosecretion, hormone release, muscle contraction, and neuronal network excitability. To investigate the selective toxicity of emodepside, we performed transgenic experiments in which the nematode SLO-1 channel was swapped for a mammalian ortholog, human KCNMA1. Expression of either the human channel or Caenorhabditis elegans slo-1 from the native slo-1 promoter in a C. elegans slo-1 functional null mutant rescued behavioral deficits that otherwise resulted from loss of slo-1 signaling. However, worms expressing the human channel were 10-to 100-fold less sensitive to emodepside than those expressing the nematode channel. Strains expressing the human KCNMA1 channel were preferentially sensitive to the mammalian channel agonists NS1619 and rottlerin. In the C. elegans pharyngeal nervous system, slo-1 is expressed in neurons, not muscle, and cell-specific rescue experiments have previously shown that emodepside inhibits serotonin-stimulated feeding by interfering with SLO-1 signaling in the nervous system. Here we show that ectopic overexpression of slo-1 in pharyngeal muscle confers sensitivity of the muscle to emodepside, consistent with a direct interaction of emodepside with the channel. Taken together, these data predict an emodepside-selective pharmacophore harbored by SLO-1. This has implications for the development of this drug/ target interface for the treatment of helminth infections.

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“…An uninsulated tungsten electrode inserted into the abdomen was used to provide a reference potential. The recording electrode consisted of a glass electrode pulled to a resistance of 2-5 M⍀ and filled (Atkinson et al, 1991;Butler et al, 1993;Meera et al, 1997). C: Table for converting between the various names used to identify alternatively spliced exons.…”

Section: Action-potential Recordingsmentioning

confidence: 99%

“…Here we show that a single slowpoke splice variant, expressed as a transgene by the slowpoke transcriptional control region, complements some, but not all, of the behavioral phenotypes. The strong conservation of slowpoke between invertebrates and vertebrates suggests that results obtained with Drosophila are useful for understanding the role of slowpoke channels in higher organisms (Butler et al, 1993).…”

mentioning

confidence: 99%

Complementation of Physiological and Behavioral Defects by a Slowpoke Ca²⁺ ‐Activated K⁺ Channel Transgene

Brenner

Srinivasan

et al. 2000

Journal of Neurochemistry

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Abstract:The Drosophila slowpoke gene encodes a large conductance calcium-activated potassium channel used in neurons, muscle, and some epithelial cells. Tissuespecific transcriptional promoters and alternative mRNA splicing generate a large array of transcripts. These distinct transcripts are thought to tailor the properties of the channel to the requirements of the cell. Presumably, a single splice variant cannot satisfy the specific needs of all cell types. To test this, we examined whether a single slowpoke splice variant was capable of complementing all slowpoke behavioral phenotypes. Null mutations in slowpoke cause animals to be semiflightless and to manifest an inducible "sticky-feet" phenotype. The well-characterized slowpoke transcriptional control region was used to direct the expression of a single slowpoke splice variant (cDNA H13) in transgenic flies. The endogenous gene in these flies had been inactivated by the slo 4 mutation. Action-potential recordings and voltage-clamp recordings demonstrated the production of functional channels from the transgene. The transgene completely complemented the flight defect, but not the sticky-feet phenotype. We conclude that distinct slowpoke channel isoforms, produced by alternative splicing, are not interchangeable and are required for proper function of different cell types. Key Words: Potassium channel-slowpoke-Drosophila-mRNA splicing-Behavior-Voltage clamp.

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mSlo , a Complex Mouse Gene Encoding "Maxi" Calcium-Activated Potassium Channels

Cited by 629 publications

References 30 publications

Flagellar ion channels of sperm: similarities and differences between species

Flagellar ion channels of sperm: similarities and differences between species

Selective Toxicity of the Anthelmintic Emodepside Revealed by Heterologous Expression of Human KCNMA1 inCaenorhabditis elegans

Complementation of Physiological and Behavioral Defects by a Slowpoke Ca²⁺ ‐Activated K⁺ Channel Transgene

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mSlo , a Complex Mouse Gene Encoding "Maxi" Calcium-Activated Potassium Channels

Cited by 629 publications

References 30 publications

Flagellar ion channels of sperm: similarities and differences between species

Flagellar ion channels of sperm: similarities and differences between species

Selective Toxicity of the Anthelmintic Emodepside Revealed by Heterologous Expression of Human KCNMA1 inCaenorhabditis elegans

Complementation of Physiological and Behavioral Defects by a Slowpoke Ca2+ ‐Activated K+ Channel Transgene

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Complementation of Physiological and Behavioral Defects by a Slowpoke Ca²⁺ ‐Activated K⁺ Channel Transgene