Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Separable effects of human Kvbeta1.2 N- and C-termini on inactivation and expression of human Kv1.4.
Accili EA, Kuryshev YA, Wible BA, Brown AM.
???displayArticle.abstract???
1. The Kvbeta subunits of voltage-gated K+ channels alter the functional expression and gating of non- or slowly inactivating Kvalpha1 subunits via two separate domains. To determine how Kvbeta subunits modulate a rapidly inactivating Kvalpha1 subunit, we did two-microelectrode voltage clamp experiments on human Kv1.4 voltage-gated K+ channels expressed heterologously in Xenopus oocytes. In addition we tested a slowly inactivating mutant of Kv1.4 lacking amino acids 2-146 of the N-terminal alpha-ball domain (Kv1. 4DeltaN2-146). Kv1.4 or Kv1.4DeltaN2-146 were co-expressed with either rat Kvbeta2 or human Kvbeta1.2. To separate domain effects, we also used a mutant of Kvbeta1.2 lacking the unique 79 amino acid N-terminal beta-ball domain (Kvbeta1-C). 2. For the mutant Kv1.4DeltaN2-146 we found that Kvbeta1-C or Kvbeta2 increased current amplitude without altering activation or inactivation. By contrast Kvbeta1.2 produced rapid inactivation and slowed deactivation due to block produced by the beta-ball. The beta-ball also increased the rate of C-type inactivation in 5 mM, but not 50 mM, external K+ consistent with an effect of blockade on K+ efflux. 3. For Kv1.4, Kvbeta1-C produced a voltage-independent increase in the rate of inactivation and shifted the inactivation curve to more hyperpolarized potentials, but had no effect on deactivation. Kvbeta1-C, Kvbeta2 and Kvbeta1.2 slowed recovery from inactivation similarly, thereby excluding involvement of the beta-ball. Kvbeta1.2 produced an additional more rapid, voltage-dependent component of inactivation, significantly reduced peak outward current and shifted steady-state inactivation towards hyperpolarized potentials. 4. Yeast two-hybrid studies showed that alpha-beta interaction was restricted to the N-terminus of Kv1.4 and the C-terminus of Kvbeta1. 2 or Kvbeta2. Direct interaction with the alpha-ball did not occur. Our interpretation is that Kvbeta1-C and Kvbeta2 enhanced N-type inactivation produced by the Kv1.4 alpha-ball allosterically. 5. We propose that Kvbeta1.2 has three effects on Kv1.4, the first two of which it shares with Kvbeta2. First, Kvbeta1-C and Kvbeta2 have a current-enhancing effect. Second, Kvbeta1-C and Kvbeta2 increase block by the alpha-ball allosterically. Third, the beta-ball of Kbeta1.2 directly blocks both Kv1.4 and Kv1.4DeltaN2-146. When both alpha- and beta-balls are present, competition for their respective binding sites slows the block produced by either ball.
Accili,
Separable Kvbeta subunit domains alter expression and gating of potassium channels.
1997, Pubmed,
Xenbase
Accili,
Separable Kvbeta subunit domains alter expression and gating of potassium channels.
1997,
Pubmed
,
Xenbase Accili,
Interactions among inactivating and noninactivating Kvbeta subunits, and Kvalpha1.2, produce potassium currents with intermediate inactivation.
1997,
Pubmed
,
Xenbase Baukrowitz,
Modulation of K+ current by frequency and external [K+]: a tale of two inactivation mechanisms.
1995,
Pubmed Bertoli,
Activation and deactivation properties of rat brain K+ channels of the Shaker-related subfamily.
1994,
Pubmed
,
Xenbase Castellino,
Time- and voltage-dependent modulation of a Kv1.4 channel by a beta-subunit (Kv beta 3) cloned from ferret ventricle.
1995,
Pubmed
,
Xenbase Connor,
Voltage clamp studies of a transient outward membrane current in gastropod neural somata.
1971,
Pubmed Debanne,
Action-potential propagation gated by an axonal I(A)-like K+ conductance in hippocampus.
1997,
Pubmed De Biasi,
Open channel block of human heart hKv1.5 by the beta-subunit hKv beta 1.2.
1997,
Pubmed
,
Xenbase England,
Characterization of a voltage-gated K+ channel beta subunit expressed in human heart.
1995,
Pubmed
,
Xenbase Heinemann,
Functional characterization of Kv channel beta-subunits from rat brain.
1996,
Pubmed
,
Xenbase Heinemann,
The inactivation behaviour of voltage-gated K-channels may be determined by association of alpha- and beta-subunits.
1994,
Pubmed
,
Xenbase Hoshi,
Two types of inactivation in Shaker K+ channels: effects of alterations in the carboxy-terminal region.
1991,
Pubmed
,
Xenbase Majumder,
Molecular cloning and functional expression of a novel potassium channel beta-subunit from human atrium.
1995,
Pubmed
,
Xenbase McCormack,
Alternative splicing of the human Shaker K+ channel beta 1 gene and functional expression of the beta 2 gene product.
1995,
Pubmed
,
Xenbase McIntosh,
Modification of rat brain Kv1.4 channel gating by association with accessory Kvbeta1.1 and beta2.1 subunits.
1997,
Pubmed
,
Xenbase Morales,
A novel beta subunit increases rate of inactivation of specific voltage-gated potassium channel alpha subunits.
1995,
Pubmed
,
Xenbase Morales,
The N-terminal domain of a K+ channel beta subunit increases the rate of C-type inactivation from the cytoplasmic side of the channel.
1996,
Pubmed
,
Xenbase Nakahira,
Selective interaction of voltage-gated K+ channel beta-subunits with alpha-subunits.
1996,
Pubmed Pardo,
Extracellular K+ specifically modulates a rat brain K+ channel.
1992,
Pubmed
,
Xenbase Rasmusson,
C-type inactivation controls recovery in a fast inactivating cardiac K+ channel (Kv1.4) expressed in Xenopus oocytes.
1995,
Pubmed
,
Xenbase Rettig,
Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit.
1994,
Pubmed
,
Xenbase Rhodes,
Association and colocalization of the Kvbeta1 and Kvbeta2 beta-subunits with Kv1 alpha-subunits in mammalian brain K+ channel complexes.
1997,
Pubmed Rhodes,
Association and colocalization of K+ channel alpha- and beta-subunit polypeptides in rat brain.
1995,
Pubmed Sewing,
Kv beta 1 subunit binding specific for shaker-related potassium channel alpha subunits.
1996,
Pubmed Shamotienko,
Subunit combinations defined for K+ channel Kv1 subtypes in synaptic membranes from bovine brain.
1997,
Pubmed Sheng,
Presynaptic A-current based on heteromultimeric K+ channels detected in vivo.
1993,
Pubmed Shi,
Beta subunits promote K+ channel surface expression through effects early in biosynthesis.
1996,
Pubmed Taglialatela,
C-terminus determinants for Mg2+ and polyamine block of the inward rectifier K+ channel IRK1.
1995,
Pubmed
,
Xenbase Tseng-Crank,
Functional role of the NH2-terminal cytoplasmic domain of a mammalian A-type K channel.
1993,
Pubmed
,
Xenbase Wang,
Comparison of binding and block produced by alternatively spliced Kvbeta1 subunits.
1996,
Pubmed Xu,
Kvbeta2 inhibits the Kvbeta1-mediated inactivation of K+ channels in transfected mammalian cells.
1997,
Pubmed Yu,
NAB domain is essential for the subunit assembly of both alpha-alpha and alpha-beta complexes of shaker-like potassium channels.
1996,
Pubmed
