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J Neurosci
2007 Jan 10;272:270-8. doi: 10.1523/JNEUROSCI.3801-06.2007.
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Slow conformational changes of the voltage sensor during the mode shift in hyperpolarization-activated cyclic-nucleotide-gated channels.
Bruening-Wright A, Larsson HP.
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Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels are activated by hyperpolarizations that cause inward movements of the positive charges in the fourth transmembrane domain (S4), which triggers channel opening. If HCN channels are held open for prolonged times (>50 ms), HCN channels undergo a mode shift, which in sea urchin (spHCN) channels induces a >50 mV shift in the midpoint of activation. The mechanism underlying the mode shift is unknown. The mode shift could be attributable to conformational changes in the pore domain that stabilize the open state of the channel, which would indirectly shift the voltage dependence of the channel, or attributable to conformational changes in the voltage-sensing domain that stabilize the inward position of S4, thereby directly shifting the voltage dependence of the channel. We used voltage-clamp fluorometry to detect S4 movements and to correlate S4 movements to the different activation steps in spHCN channels. We here show that fluorophores attached to S4 report on fluorescence changes during the mode shift, demonstrating that the mode shift is not simply attributable to a stabilization of the pore domain but that S4 undergoes conformational changes during the mode shift. We propose a model in which the mode shift is attributable to a slow, lateral movement in S4 that is triggered by the initial S4 gating-charge movement and channel opening. The mode shift gives rise to a short-term, activity-dependent memory in HCN channels, which has been shown previously to be important for the stable rhythmic firing of pacemaking neurons and could significantly affect synaptic integration.
Bell,
Changes in local S4 environment provide a voltage-sensing mechanism for mammalian hyperpolarization-activated HCN channels.
2004, Pubmed,
Xenbase
Bell,
Changes in local S4 environment provide a voltage-sensing mechanism for mammalian hyperpolarization-activated HCN channels.
2004,
Pubmed
,
Xenbase Cha,
Characterizing voltage-dependent conformational changes in the Shaker K+ channel with fluorescence.
1997,
Pubmed
,
Xenbase Chen,
Properties of hyperpolarization-activated pacemaker current defined by coassembly of HCN1 and HCN2 subunits and basal modulation by cyclic nucleotide.
2001,
Pubmed
,
Xenbase DiFrancesco,
Pacemaker mechanisms in cardiac tissue.
1993,
Pubmed Elinder,
Mode shifts in the voltage gating of the mouse and human HCN2 and HCN4 channels.
2006,
Pubmed
,
Xenbase Gandhi,
Reconstructing voltage sensor-pore interaction from a fluorescence scan of a voltage-gated K+ channel.
2000,
Pubmed Gauss,
Molecular identification of a hyperpolarization-activated channel in sea urchin sperm.
1998,
Pubmed Hille,
Ion channels: from idea to reality.
1999,
Pubmed Johnson,
The carboxyl-terminal region of cyclic nucleotide-modulated channels is a gating ring, not a permeation path.
2005,
Pubmed
,
Xenbase Larsson,
Fluorometric measurements of conformational changes in glutamate transporters.
2004,
Pubmed
,
Xenbase Li,
Early fluorescence signals detect transitions at mammalian serotonin transporters.
2002,
Pubmed
,
Xenbase Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed Loots,
Molecular coupling of S4 to a K(+) channel's slow inactivation gate.
2000,
Pubmed Loots,
Protein rearrangements underlying slow inactivation of the Shaker K+ channel.
1998,
Pubmed Ludwig,
Absence epilepsy and sinus dysrhythmia in mice lacking the pacemaker channel HCN2.
2003,
Pubmed Magee,
Dendritic voltage-gated ion channels regulate the action potential firing mode of hippocampal CA1 pyramidal neurons.
1999,
Pubmed Magee,
Dendritic hyperpolarization-activated currents modify the integrative properties of hippocampal CA1 pyramidal neurons.
1998,
Pubmed Männikkö,
Hysteresis in the voltage dependence of HCN channels: conversion between two modes affects pacemaker properties.
2005,
Pubmed
,
Xenbase Männikkö,
Voltage-sensing mechanism is conserved among ion channels gated by opposite voltages.
2002,
Pubmed
,
Xenbase Mannuzzu,
Direct physical measure of conformational rearrangement underlying potassium channel gating.
1996,
Pubmed
,
Xenbase Nolan,
The hyperpolarization-activated HCN1 channel is important for motor learning and neuronal integration by cerebellar Purkinje cells.
2003,
Pubmed Olcese,
Correlation between charge movement and ionic current during slow inactivation in Shaker K+ channels.
1997,
Pubmed
,
Xenbase Olcese,
A conducting state with properties of a slow inactivated state in a shaker K(+) channel mutant.
2001,
Pubmed
,
Xenbase Pape,
Queer current and pacemaker: the hyperpolarization-activated cation current in neurons.
1996,
Pubmed Pathak,
The cooperative voltage sensor motion that gates a potassium channel.
2005,
Pubmed
,
Xenbase Robinson,
Hyperpolarization-activated cation currents: from molecules to physiological function.
2003,
Pubmed Rothberg,
Voltage-controlled gating at the intracellular entrance to a hyperpolarization-activated cation channel.
2002,
Pubmed Santoro,
The HCN gene family: molecular basis of the hyperpolarization-activated pacemaker channels.
1999,
Pubmed Schulze-Bahr,
Pacemaker channel dysfunction in a patient with sinus node disease.
2003,
Pubmed Shin,
Inactivation in HCN channels results from reclosure of the activation gate: desensitization to voltage.
2004,
Pubmed Ueda,
Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia.
2004,
Pubmed Ulens,
Regulation of hyperpolarization-activated HCN channels by cAMP through a gating switch in binding domain symmetry.
2003,
Pubmed
,
Xenbase Vemana,
S4 movement in a mammalian HCN channel.
2004,
Pubmed
,
Xenbase Wainger,
Molecular mechanism of cAMP modulation of HCN pacemaker channels.
2001,
Pubmed Wang,
Regulation of hyperpolarization-activated HCN channel gating and cAMP modulation due to interactions of COOH terminus and core transmembrane regions.
2001,
Pubmed
,
Xenbase Wang,
Activity-dependent regulation of HCN pacemaker channels by cyclic AMP: signaling through dynamic allosteric coupling.
2002,
Pubmed
,
Xenbase
