A Marriage of Convenience: β-Subunits and Voltage-dependent K+ Channels

Torres, Yolima P.; Morera, Francisco J.; Carvacho, Ingrid; Latorre, Ramón

doi:10.1074/jbc.r700022200

Cited by 107 publications

(106 citation statements)

References 57 publications

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“…Functional diversity of BK channels is in part conferred by cellspecific assembly of pore-forming Slo1 subunits with various auxiliary β and γ subunits (2,34). We showed previously that DHA increased currents through native BK channels in vascular smooth muscle cells as well as heterologously expressed Slo1+β1 channels (27).…”

Section: Resultsmentioning

confidence: 99%

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA

Hoshi

Tian

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Large-conductance Ca 2+ -and voltage-activated K + (BK) channels are well known for their functional versatility, which is bestowed in part by their rich modulatory repertoire. We recently showed that long-chain omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) found in oily fish lower blood pressure by activating vascular BK channels made of Slo1+β1 subunits. Here we examined the action of DHA on BK channels with different auxiliary subunit compositions. Neuronal Slo1+β4 channels were just as well activated by DHA as vascular Slo1+β1 channels. In contrast, the stimulatory effect of DHA was much smaller in Slo1+β2, Slo1+LRRC26 (γ1), and Slo1 channels without auxiliary subunits. Mutagenesis of β1, β2, and β4 showed that the large effect of DHA in Slo1+β1 and Slo1+β4 is conferred by the presence of two residues, one in the N terminus and the other in the first transmembrane segment of the β1 and β4 subunits. Transfer of this amino acid pair from β1 or β4 to β2 introduces a large response to DHA in Slo1+β2. The presence of a pair of oppositely charged residues at the aforementioned positions in β subunits is associated with a large response to DHA. The Slo1 auxiliary subunits are expressed in a highly tissue-dependent fashion. Thus, the subunit composition-dependent stimulation by DHA demonstrates that BK channels are effectors of omega-3 fatty acids with marked tissue specificity.K Ca 1.1 | fish oil | lipids

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Section: Resultsmentioning

confidence: 99%

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA

Hoshi

Tian

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…[1][2][3][4][5][6] The α-subunits exhibit a modular architecture including three characteristic domains: a tetramerization domain (T1), a voltage-sensing domain (VSD) and a pore domain (PD). [7][8][9] The membrane-embedded VSD and PD are essential for voltagedependent gating, 10 whereas the cytoplasmic T1 domain plays multiple regulatory and structural roles.…”

Section: Introductionmentioning

confidence: 99%

The dipeptidyl-aminopeptidase-like protein 6 is an integral voltage sensor-interacting β-subunit of neuronal K_V4.2 channels

Dougherty

Tu²,

Deutsch³

et al. 2009

Channels

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Auxiliary β-subunits dictate the physiological properties of voltage-gated K + (K V ) channels in excitable tissues. In many instances, however, the underlying mechanisms of action are poorly understood. The dipeptidyl-aminopeptidase-like protein 6 (DPP6) is a specific β-subunit of neuronal K V 4 channels, which may promote gating through interactions between the single transmembrane segment of DPP6 and the channel's voltage sensing domain (VSD). A combination of gating current measurements and protein biochemistry (in-vitro translation and co-immunoprecipitations) revealed preferential physical interaction between the isolated K V 4.2-VSD and DPP6. Significantly weaker interactions were detected between DPP6 and K V 1.3 channels or the K V 4.2 pore domain. More efficient gating charge movement resulting from a direct interaction between DPP6 and the K V 4.2-VSD is unique among the known actions of K V channel β-subunits. This study shows that the modular VSD of a K V channel can be directly regulated by transmembrane protein-protein interactions involving an extrinsic β-subunit. Understanding these interactions may shed light on the pathophysiology of recently identified human disorders associated with mutations affecting the dpp6 gene.

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“…This signaling is essential for fine-tuning cell excitability levels to generate appropriate responses and is partially accomplished by a variety of K + channels. Organisms have a large number of K + channels that have multiple isoforms and ancillary subunits (Salkoff et al 2006;Torres et al 2007;Fodor and Aldrich 2009). In excitable cells, a few K + channel types are responsible for the maintenance of depolarization; the rest are proposed to be modifiers, fine-tuning the particular cell or cell type for its specific function (Bargmann 1998;Santi et al 2003).…”

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confidence: 99%

Cell Excitability Necessary for Male Mating Behavior inCaenorhabditis elegansIs Coordinated by Interactions Between Big Current and Ether-A-Go-Go Family K+ Channels

LeBoeuf

García

2012

Genetics

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Variations in K + channel composition allow for differences in cell excitability and, at an organismal level, provide flexibility to behavioral regulation. When the function of a K + channel is disrupted, the remaining K + channels might incompletely compensate, manifesting as abnormal organismal behavior. In this study, we explored how different K + channels interact to regulate the neuromuscular circuitry used by Caenorhabditis elegans males to protract their copulatory spicules from their tail and insert them into the hermaphrodite's vulva during mating. We determined that the big current K + channel (BK)/SLO-1 genetically interacts with ether-a-gogo (EAG)/EGL-2 and EAG-related gene/UNC-103 K + channels to control spicule protraction. Through rescue experiments, we show that specific slo-1 isoforms affect spicule protraction. Gene expression studies show that slo-1 and egl-2 expression can be upregulated in a calcium/calmodulin-dependent protein kinase II-dependent manner to compensate for the loss of unc-103 and conversely, unc-103 can partially compensate for the loss of SLO-1 function. In conclusion, an interaction between BK and EAG family K + channels produces the muscle excitability levels that regulate the timing of spicule protraction and the success of male mating behavior.

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A Marriage of Convenience: β-Subunits and Voltage-dependent K+ Channels

Cited by 107 publications

References 57 publications

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA

The dipeptidyl-aminopeptidase-like protein 6 is an integral voltage sensor-interacting β-subunit of neuronal K_V4.2 channels

Cell Excitability Necessary for Male Mating Behavior inCaenorhabditis elegansIs Coordinated by Interactions Between Big Current and Ether-A-Go-Go Family K+ Channels

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A Marriage of Convenience: β-Subunits and Voltage-dependent K+ Channels

Cited by 107 publications

References 57 publications

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA

The dipeptidyl-aminopeptidase-like protein 6 is an integral voltage sensor-interacting β-subunit of neuronal KV4.2 channels

Cell Excitability Necessary for Male Mating Behavior inCaenorhabditis elegansIs Coordinated by Interactions Between Big Current and Ether-A-Go-Go Family K+ Channels

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The dipeptidyl-aminopeptidase-like protein 6 is an integral voltage sensor-interacting β-subunit of neuronal K_V4.2 channels