2004
DOI: 10.1074/jbc.m308070200
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The SK3 Subunit of Small Conductance Ca2+-activated K+ Channels Interacts with Both SK1 and SK2 Subunits in a Heterologous Expression System

Abstract: The aim of this study was to determine whether functional heteromeric channels can be formed by co-assembly of rat SK3 (rSK3) potassium channel subunits with either SK1 or SK2 subunits. First, to determine whether rSK3 could co-assemble with rSK2 we created rSK3VK (an SK3 mutant insensitive to block by UCL 1848). When rSK3VK was co-expressed with rSK2 the resulting currents had an intermediate sensitivity to UCL 1848 (IC 50 of ϳ5 nM compared with 120 pM for rSK2 and >300 nM for rSK3VK), suggesting that rSK3 an… Show more

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Cited by 88 publications
(90 citation statements)
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References 30 publications
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“…Since tetramerizing-coiled-coiled domains form stable tetramers (50) and the DIS is essential to the dominant-inhibitory activity of SK3-1C, DIS-dependent subunit-interactions are likely to underlie negative-dominance. Consistent with this notion, a nonfunctional SK1 mutant (hSK1YP) was recently reported to suppress SK3 channels in a dominant-negative manner by co-assembling with SK3 proteins (58). These results support a model in which non-functional isoforms of SK Ca /IK Ca channels regulate their functional counterparts, and consequently, the cellular functions that depend on them, by interfering with channel assembly and surface expression.…”
Section: Dominant-negative Suppression By Sk3-1c Is Associated With Isupporting
confidence: 71%
“…Since tetramerizing-coiled-coiled domains form stable tetramers (50) and the DIS is essential to the dominant-inhibitory activity of SK3-1C, DIS-dependent subunit-interactions are likely to underlie negative-dominance. Consistent with this notion, a nonfunctional SK1 mutant (hSK1YP) was recently reported to suppress SK3 channels in a dominant-negative manner by co-assembling with SK3 proteins (58). These results support a model in which non-functional isoforms of SK Ca /IK Ca channels regulate their functional counterparts, and consequently, the cellular functions that depend on them, by interfering with channel assembly and surface expression.…”
Section: Dominant-negative Suppression By Sk3-1c Is Associated With Isupporting
confidence: 71%
“…This is of particular relevance when it is considered that subtypes of SK channels show overlapping expression patterns in the nervous system and periphery. It is known that each SK channel subtype can form heteromeric channels with each other subtype (5,21), and it is the presence of heteromeric SK channels that introduces a new level of complication to the development of treatments targeting SK channels. Previous studies have focused on the development of subtype-specific blockers, assuming the native population of SK channels would be primarily homomeric.…”
Section: Discussionmentioning
confidence: 99%
“…Functional K Ca channels result mostly in homomeric or heteromeric assemblies of a subunits. There are three isoforms of smallconductance KCa a subunits, named SK1, SK2, and SK3, which associate to form homotetramers or heterotetramers (7,8). SK1, SK2, and SK3 proteins are principally expressed in central neurons where small-conductance KCa channels have a fundamental role in regulating neuronal excitability (9).…”
Section: Introductionmentioning
confidence: 99%