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.
???displayArticle.abstract???
Mechanoelectric feedback in heart and smooth muscle is thought to depend on diverse channels that afford myocytes a mechanosensitive cation conductance. Voltage-gated channels (e.g., Kv1) are stretch sensitive, but the only voltage-gated channels that are cation permeant, the pacemaker or HCN (hyperpolarization-activated cyclic nucleotide-gated) channels, have not been tested. To assess if HCN channels could contribute to a mechanosensitive cation conductance, we recorded I(HCN) in cell-attached oocyte patches before, during, and after stretch for a range of voltage protocols. I(mHCN2) has voltage-dependent and instantaneous components; only the former was stretch sensitive. Stretch reversibly accelerated hyperpolarization-induced I(mHCN2) activation (likewise for I(spHCN)) and depolarization-induced deactivation. HCN channels (like Kv1 channels) undergo mode-switch transitions that render their activation midpoints voltage history dependent. The result, as seen from sawtooth clamp, is a pronounced hysteresis. During sawtooth clamp, stretch increased current magnitudes and altered the hysteresis pattern consistent with stretch-accelerated activation and deactivation. I(mHCN2) responses to step protocols indicated that at least two transitions were mechanosensitive: an unspecified rate-limiting transition along the hyperpolarization-driven path, mode I(closed)-->mode II(open), and depolarization-induced deactivation (from mode I(open) and/or from mode II(open)). How might this affect cardiac rhythmicity? Since hysteresis patterns and "on" and "off" I(HCN) responses all changed with stretch, predictions are difficult. For an empirical overview, we therefore clamped patches to cyclic action potential waveforms. During the diastolic potential of sinoatrial node cell and Purkinje fiber waveforms, net stretch effects were frequency dependent. Stretch-inhibited (SI) I(mHCN2) dominated at low frequencies and stretch-augmented (SA) I(mHCN2) was progressively more important as frequency increased. HCN channels might therefore contribute to either SI or SA cation conductances that in turn contribute to stretch arrhythmias and other mechanoelectric feedback phenomena.
Arhem,
Voltage sensing in ion channels: a 50-year-old mystery resolved?
2004, Pubmed
Arhem,
Voltage sensing in ion channels: a 50-year-old mystery resolved?
2004,
Pubmed Arinsburg,
Constitutively active Src tyrosine kinase changes gating of HCN4 channels through direct binding to the channel proteins.
2006,
Pubmed Azene,
Non-equilibrium behavior of HCN channels: insights into the role of HCN channels in native and engineered pacemakers.
2005,
Pubmed
,
Xenbase Bahri,
Quantification of lipid bilayer effective microviscosity and fluidity effect induced by propofol.
2005,
Pubmed Barbuti,
Localization of pacemaker channels in lipid rafts regulates channel kinetics.
2004,
Pubmed Baruscotti,
Physiology and pharmacology of the cardiac pacemaker ("funny") current.
2005,
Pubmed Calabrese,
Mechanosensitivity of N-type calcium channel currents.
2002,
Pubmed Calloe,
Hypoosmotic cell swelling as a novel mechanism for modulation of cloned HCN2 channels.
2005,
Pubmed
,
Xenbase Cantor,
Size distribution of barrel-stave aggregates of membrane peptides: influence of the bilayer lateral pressure profile.
2002,
Pubmed Chen,
Suppression of ih contributes to propofol-induced inhibition of mouse cortical pyramidal neurons.
2005,
Pubmed
,
Xenbase Chen,
HCN subunit-specific and cAMP-modulated effects of anesthetics on neuronal pacemaker currents.
2005,
Pubmed Chen,
Properties of hyperpolarization-activated pacemaker current defined by coassembly of HCN1 and HCN2 subunits and basal modulation by cyclic nucleotide.
2001,
Pubmed
,
Xenbase Cho,
Hyperpolarization-activated, cyclic AMP-gated, HCN1-like cation channel: the primary, full-length HCN isoform expressed in a saccular hair-cell layer.
2003,
Pubmed Cohen,
Pacemaker current and automatic rhythms: toward a molecular understanding.
2006,
Pubmed Cooper,
Species- and preparation-dependence of stretch effects on sino-atrial node pacemaking.
2005,
Pubmed Cuello,
Molecular architecture of the KvAP voltage-dependent K+ channel in a lipid bilayer.
2004,
Pubmed del Camino,
Status of the intracellular gate in the activated-not-open state of shaker K+ channels.
2005,
Pubmed
,
Xenbase DiFrancesco,
Serious workings of the funny current.
2006,
Pubmed Doan,
Differential distribution and function of hyperpolarization-activated channels in sensory neurons and mechanosensitive fibers.
2004,
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 Ghamari-Langroudi,
Excitatory role of the hyperpolarization-activated inward current in phasic and tonic firing of rat supraoptic neurons.
2000,
Pubmed Giles,
Supraventricular pacemaker activity in the canine heart: contributions from HCN channels in control conditions and in a model of heart failure.
2005,
Pubmed Gill,
Characterization of the human HCN1 channel and its inhibition by capsazepine.
2004,
Pubmed Greenwood,
Characteristics of hyperpolarization-activated cation currents in portal vein smooth muscle cells.
2002,
Pubmed Gu,
Stretch-activation and stretch-inactivation of Shaker-IR, a voltage-gated K+ channel.
2001,
Pubmed
,
Xenbase Guo,
Effects of sphingosine 1-phosphate on pacemaker activity in rabbit sino-atrial node cells.
1999,
Pubmed Hisada,
Hyperpolarization-activated cationic channels in smooth muscle cells are stretch sensitive.
1991,
Pubmed Hu,
[Effect of lysophosphatidylcholine on the pacemaker current I(f) of sheep cardial Purkinje fibers in ischemia-like condition].
1997,
Pubmed Hurwitz,
A mechanogated nonselective cation channel in proximal tubule that is ATP sensitive.
2002,
Pubmed Kroin,
Clonidine prolongation of lidocaine analgesia after sciatic nerve block in rats Is mediated via the hyperpolarization-activated cation current, not by alpha-adrenoreceptors.
2004,
Pubmed Laitko,
Membrane tension accelerates rate-limiting voltage-dependent activation and slow inactivation steps in a Shaker channel.
2004,
Pubmed
,
Xenbase Laitko,
Membrane stretch slows the concerted step prior to opening in a Kv channel.
2006,
Pubmed
,
Xenbase Lee,
Hyperpolarization-activated, cation-nonselective, cyclic nucleotide-modulated channel blockade alleviates mechanical allodynia and suppresses ectopic discharge in spinal nerve ligated rats.
2005,
Pubmed Liu,
A novel osmosensitive voltage gated cation current in rat supraoptic neurones.
2005,
Pubmed Long,
Voltage sensor of Kv1.2: structural basis of electromechanical coupling.
2005,
Pubmed Loots,
Molecular coupling of S4 to a K(+) channel's slow inactivation gate.
2000,
Pubmed Ludwig,
Absence epilepsy and sinus dysrhythmia in mice lacking the pacemaker channel HCN2.
2003,
Pubmed Lundbaek,
Capsaicin regulates voltage-dependent sodium channels by altering lipid bilayer elasticity.
2005,
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 Matsuyoshi,
Expression of hyperpolarization-activated cyclic nucleotide-gated cation channels in rat dorsal root ganglion neurons innervating urinary bladder.
2006,
Pubmed Monteggia,
Cloning and localization of the hyperpolarization-activated cyclic nucleotide-gated channel family in rat brain.
2000,
Pubmed Morris,
Studying the mechanosensitivity of voltage-gated channels using oocyte patches.
2006,
Pubmed
,
Xenbase Morris,
Lipid stress at play: mechanosensitivity of voltage-gated channels.
2007,
Pubmed Notomi,
Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain.
2004,
Pubmed Okamoto,
Hyperpolarization-activated cation current (Ih) is an ethanol target in midbrain dopamine neurons of mice.
2006,
Pubmed Olcese,
A conducting state with properties of a slow inactivated state in a shaker K(+) channel mutant.
2001,
Pubmed
,
Xenbase Papp,
Hyperpolarization-activated and cyclic nucleotide-gated cation channel subunit 2 ion channels modulate synaptic transmission from nociceptive primary afferents containing substance P to secondary sensory neurons in laminae I-IIo of the rodent spinal dorsal horn.
2006,
Pubmed Pathak,
The cooperative voltage sensor motion that gates a potassium channel.
2005,
Pubmed
,
Xenbase Proenza,
Distinct populations of HCN pacemaker channels produce voltage-dependent and voltage-independent currents.
2006,
Pubmed Qu,
Functional comparison of HCN isoforms expressed in ventricular and HEK 293 cells.
2002,
Pubmed Qu,
MiRP1 modulates HCN2 channel expression and gating in cardiac myocytes.
2004,
Pubmed Seifert,
Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis.
1999,
Pubmed Sharif Naeini,
An N-terminal variant of Trpv1 channel is required for osmosensory transduction.
2006,
Pubmed Suchyna,
Identification of a peptide toxin from Grammostola spatulata spider venom that blocks cation-selective stretch-activated channels.
2000,
Pubmed Sung,
Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart.
2003,
Pubmed Tu,
Hyperpolarization-activated, cyclic nucleotide-gated cation channels: roles in the differential electrophysiological properties of rat primary afferent neurons.
2004,
Pubmed Wiggins,
Membrane-protein interactions in mechanosensitive channels.
2005,
Pubmed Xiao,
Molecular and functional analysis of hyperpolarisation-activated nucleotide-gated (HCN) channels in the enteric nervous system.
2004,
Pubmed Ying,
Propofol block of I(h) contributes to the suppression of neuronal excitability and rhythmic burst firing in thalamocortical neurons.
2006,
Pubmed Yu,
Calcium influx through hyperpolarization-activated cation channels (I(h) channels) contributes to activity-evoked neuronal secretion.
2004,
Pubmed Zabel,
Stretch-induced voltage changes in the isolated beating heart: importance of the timing of stretch and implications for stretch-activated ion channels.
1996,
Pubmed Zicha,
Sinus node dysfunction and hyperpolarization-activated (HCN) channel subunit remodeling in a canine heart failure model.
2005,
Pubmed
