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Biophys J
2012 Oct 03;1037:1440-50. doi: 10.1016/j.bpj.2012.08.036.
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Interaction of the S6 proline hinge with N-type and C-type inactivation in Kv1.4 channels.
Bett GC
,
Lis A
,
Guo H
,
Liu M
,
Zhou Q
,
Rasmusson RL
.
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Several voltage-gated channels share a proline-valine-proline (proline hinge) sequence motif at the intracellular side of S6. We studied the proline hinge in Kv1.4 channels, which inactivate via two mechanisms: N- and C-type. We mutated the second proline to glycine or alanine: P558A, P558G. These mutations were studied in the presence/absence of the N-terminal to separate the effects of the interaction between the proline hinge and N- and C-type inactivation. Both S6 mutations slowed or removed N- and C-type inactivation, and altered recovery from inactivation. P558G slowed activation and N- and C-type inactivation by nearly an order of magnitude. Sensitivity to extracellular acidosis and intracellular quinidine binding remained, suggesting that transmembrane communication in N- and C-type inactivation was preserved, consistent with our previous findings of major structural rearrangements involving S6 during C-type inactivation. P558A was very disruptive: activation was slowed by more than an order of magnitude, and no inactivation was observed. These results are consistent with our hypothesis that the proline hinge and intracellular S6 movement play a significant role in inactivation and recovery. Computer modeling suggests that both P558G and P558A mutations modify early voltage-dependent steps and make a final voltage-insensitive step that is rate limiting at positive potentials.
Adelman,
Episodic ataxia results from voltage-dependent potassium channels with altered functions.
1995, Pubmed,
Xenbase
Adelman,
Episodic ataxia results from voltage-dependent potassium channels with altered functions.
1995,
Pubmed
,
Xenbase
Armstrong,
Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons.
1971,
Pubmed
Barry,
Myocardial potassium channels: electrophysiological and molecular diversity.
1996,
Pubmed
Baukrowitz,
Modulation of K+ current by frequency and external [K+]: a tale of two inactivation mechanisms.
1995,
Pubmed
Baukrowitz,
Use-dependent blockers and exit rate of the last ion from the multi-ion pore of a K+ channel.
1996,
Pubmed
Bett,
Modification of K+ channel-drug interactions by ancillary subunits.
2008,
Pubmed
Bett,
A model of the interaction between N-type and C-type inactivation in Kv1.4 channels.
2011,
Pubmed
,
Xenbase
Bett,
Inactivation and recovery in Kv1.4 K+ channels: lipophilic interactions at the intracellular mouth of the pore.
2004,
Pubmed
,
Xenbase
Bezanilla,
Voltage sensor movements.
2002,
Pubmed
Busch,
Current inactivation involves a histidine residue in the pore of the rat lymphocyte potassium channel RGK5.
1991,
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
Choi,
Tetraethylammonium blockade distinguishes two inactivation mechanisms in voltage-activated K+ channels.
1991,
Pubmed
Claydon,
Inhibition of the K+ channel kv1.4 by acidosis: protonation of an extracellular histidine slows the recovery from N-type inactivation.
2000,
Pubmed
,
Xenbase
Comer,
Cloning and characterization of an Ito-like potassium channel from ferret ventricle.
1994,
Pubmed
,
Xenbase
Consiglio,
Influence of permeant ions on voltage sensor function in the Kv2.1 potassium channel.
2004,
Pubmed
Cuello,
Structural basis for the coupling between activation and inactivation gates in K(+) channels.
2010,
Pubmed
Ding,
Investigating the putative glycine hinge in Shaker potassium channel.
2005,
Pubmed
,
Xenbase
Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed
Hackos,
Scanning the intracellular S6 activation gate in the shaker K+ channel.
2002,
Pubmed
,
Xenbase
Holmgren,
N-type inactivation and the S4-S5 region of the Shaker K+ channel.
1996,
Pubmed
Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase
Hoshi,
Two types of inactivation in Shaker K+ channels: effects of alterations in the carboxy-terminal region.
1991,
Pubmed
,
Xenbase
Imbrici,
Contribution of the central hydrophobic residue in the PXP motif of voltage-dependent K+ channels to S6 flexibility and gating properties.
2009,
Pubmed
,
Xenbase
Isacoff,
Putative receptor for the cytoplasmic inactivation gate in the Shaker K+ channel.
1991,
Pubmed
,
Xenbase
Jan,
Structural elements involved in specific K+ channel functions.
1992,
Pubmed
Jerng,
K+ channel inactivation mediated by the concerted action of the cytoplasmic N- and C-terminal domains.
1997,
Pubmed
,
Xenbase
Jiang,
Crystal structure and mechanism of a calcium-gated potassium channel.
2002,
Pubmed
Jiang,
C-type inactivation involves a significant decrease in the intracellular aqueous pore volume of Kv1.4 K+ channels expressed in Xenopus oocytes.
2003,
Pubmed
,
Xenbase
Kehl,
Molecular determinants of the inhibition of human Kv1.5 potassium currents by external protons and Zn(2+).
2002,
Pubmed
Kiss,
Modulation of C-type inactivation by K+ at the potassium channel selectivity filter.
1998,
Pubmed
Korovkina,
Molecular diversity of vascular potassium channel isoforms.
2002,
Pubmed
Kurata,
A structural interpretation of voltage-gated potassium channel inactivation.
2006,
Pubmed
Labro,
Gating of shaker-type channels requires the flexibility of S6 caused by prolines.
2003,
Pubmed
Larsson,
Transmembrane movement of the shaker K+ channel S4.
1996,
Pubmed
,
Xenbase
Li,
Regulation of N- and C-type inactivation of Kv1.4 by pHo and K+: evidence for transmembrane communication.
2003,
Pubmed
,
Xenbase
Lipkind,
A structural motif for the voltage-gated potassium channel pore.
1995,
Pubmed
Liu,
Dynamic rearrangement of the outer mouth of a K+ channel during gating.
1996,
Pubmed
Long,
Voltage sensor of Kv1.2: structural basis of electromechanical coupling.
2005,
Pubmed
Lopez,
Evidence that the S6 segment of the Shaker voltage-gated K+ channel comprises part of the pore.
1994,
Pubmed
,
Xenbase
López-Barneo,
Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.
1993,
Pubmed
,
Xenbase
Mitcheson,
Structural determinants for high-affinity block of hERG potassium channels.
2005,
Pubmed
Ogielska,
Functional consequences of a decreased potassium affinity in a potassium channel pore. Ion interactions and C-type inactivation.
1999,
Pubmed
,
Xenbase
Panyi,
C-type inactivation of a voltage-gated K+ channel occurs by a cooperative mechanism.
1995,
Pubmed
Panyi,
Cross talk between activation and slow inactivation gates of Shaker potassium channels.
2006,
Pubmed
Panyi,
Probing the cavity of the slow inactivated conformation of shaker potassium channels.
2007,
Pubmed
Rasmusson,
Inactivation of voltage-gated cardiac K+ channels.
1998,
Pubmed
Raybaud,
The role of the GX9GX3G motif in the gating of high voltage-activated Ca2+ channels.
2006,
Pubmed
,
Xenbase
Sheng,
Subcellular segregation of two A-type K+ channel proteins in rat central neurons.
1992,
Pubmed
,
Xenbase
Wang,
Kv1.4 channel block by quinidine: evidence for a drug-induced allosteric effect.
2003,
Pubmed
,
Xenbase
Zagotta,
Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB.
1990,
Pubmed
,
Xenbase
Zhao,
A gating hinge in Na+ channels; a molecular switch for electrical signaling.
2004,
Pubmed
del Camino,
Blocker protection in the pore of a voltage-gated K+ channel and its structural implications.
2000,
Pubmed
