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.
J Membr Biol
2015 Feb 01;2481:67-81. doi: 10.1007/s00232-014-9742-0.
Show Gene links
Show Anatomy links
HCN2 channels: a permanent open state and conductance changes.
Pittoors F
,
Van Bogaert PP
.
???displayArticle.abstract???
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the membranes of heart and brain cells can conduct Na(+) and K(+) ions and activate between -30 and -120 mV. We express the α subunit of HCN2 channels in Xenopus laevis oocytes and are confronted with two unexpected problems. First, we observe a rise in membrane conductance at resting potential proportional to the amount of expression. On activation to hyperpolarizing potentials, the instantaneous conductance rises in proportion to the amount of activated current. CsCl reduces the observed effects. This can be explained by the expression in oocytes membranes of a fraction of permanently open HCN2 channels. Second, using TEVC technique, our data show a completely different behaviour in physiological solutions of heterogeneously expressed HCN2 currents from what is observed in wild-type currents in the absence of drugs. During pulse trains, we frequently observe (1) a fast and significant decline of the amplitude of HCN2 current during hyperpolarizing steps, (2) no recovery of this decline after a long period at resting membrane potential, (3) a different behaviour of the tail currents at depolarization with other and slower changes than during activation, (4) recovery of this decline in high K(+)/low Na(+) bath solution. The decline of the HCN2 current in physiological conditions is caused by a reduction of the conductance of the HCN2 channel presumably caused by the mere presence of sodium in the channel, in competition with potassium ions and with a limitative effect on the channel conductance.
Almers,
Potassium conductance changes in skeletal muscle and the potassium concentration in the transverse tubules.
1972, Pubmed
Almers,
Potassium conductance changes in skeletal muscle and the potassium concentration in the transverse tubules.
1972,
Pubmed
Almers,
The decline of potassium permeability during extreme hyperpolarization in frog skeletal muscle.
1972,
Pubmed
Au,
Structural and functional determinants in the S5-P region of HCN-encoded pacemaker channels revealed by cysteine-scanning substitutions.
2008,
Pubmed
,
Xenbase
Azene,
Non-equilibrium behavior of HCN channels: insights into the role of HCN channels in native and engineered pacemakers.
2005,
Pubmed
,
Xenbase
Azene,
Pore-to-gate coupling of HCN channels revealed by a pore variant that contributes to gating but not permeation.
2005,
Pubmed
,
Xenbase
Azene,
Molecular basis of the effect of potassium on heterologously expressed pacemaker (HCN) channels.
2003,
Pubmed
,
Xenbase
Barish,
A transient calcium-dependent chloride current in the immature Xenopus oocyte.
1983,
Pubmed
,
Xenbase
Baumgarten,
Depletion and accumulation of potassium in the extracellular clefts of cardiac Purkinje fibers during voltage clamp hyperpolarization and depolarization.
1977,
Pubmed
Baumgarten,
Depletion and accumulation of potassium in the extracellular clefts of cardiac Purkinje fibers during voltage clamp hyperpolarization and depolarization: experiments in sodium-free bathing media.
1977,
Pubmed
Belles,
"Run-down" of the Ca current during long whole-cell recordings in guinea pig heart cells: role of phosphorylation and intracellular calcium.
1988,
Pubmed
BoSmith,
Inhibitory actions of ZENECA ZD7288 on whole-cell hyperpolarization activated inward current (If) in guinea-pig dissociated sinoatrial node cells.
1993,
Pubmed
Bois,
Mode of action of bradycardic agent, S 16257, on ionic currents of rabbit sinoatrial node cells.
1996,
Pubmed
Brown,
A tribute to the Xenopus laevis oocyte and egg.
2004,
Pubmed
,
Xenbase
Bucchi,
Current-dependent block of rabbit sino-atrial node I(f) channels by ivabradine.
2002,
Pubmed
Byerly,
Intracellular factors for the maintenance of calcium currents in perfused neurones from the snail, Lymnaea stagnalis.
1986,
Pubmed
Callewaert,
Single cardiac Purkinje cells: general electrophysiology and voltage-clamp analysis of the pace-maker current.
1984,
Pubmed
Chen,
The S4-S5 linker couples voltage sensing and activation of pacemaker channels.
2001,
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
Chen,
Functional roles of charged residues in the putative voltage sensor of the HCN2 pacemaker channel.
2000,
Pubmed
,
Xenbase
Cheng,
Molecular mapping of the binding site for a blocker of hyperpolarization-activated, cyclic nucleotide-modulated pacemaker channels.
2007,
Pubmed
,
Xenbase
Costa,
Determination of ionic permeability coefficients of the plasma membrane of Xenopus laevis oocytes under voltage clamp.
1989,
Pubmed
,
Xenbase
Dascal,
The use of Xenopus oocytes for the study of ion channels.
1987,
Pubmed
,
Xenbase
Decher,
Voltage-dependent gating of hyperpolarization-activated, cyclic nucleotide-gated pacemaker channels: molecular coupling between the S4-S5 and C-linkers.
2004,
Pubmed
,
Xenbase
Decher,
KCNE2 modulates current amplitudes and activation kinetics of HCN4: influence of KCNE family members on HCN4 currents.
2003,
Pubmed
,
Xenbase
Deitmer,
Interactions between the regulation of the intracellular pH and sodium activity of sheep cardiac Purkinje fibres.
1980,
Pubmed
DiFrancesco,
Characterization of single pacemaker channels in cardiac sino-atrial node cells.
,
Pubmed
DiFrancesco,
Properties of the hyperpolarizing-activated current (if) in cells isolated from the rabbit sino-atrial node.
1986,
Pubmed
DiFrancesco,
Block and activation of the pace-maker channel in calf purkinje fibres: effects of potassium, caesium and rubidium.
1982,
Pubmed
DiFrancesco,
The cardiac hyperpolarizing-activated current, if. Origins and developments.
1985,
Pubmed
DiFrancesco,
Some properties of the UL-FS 49 block of the hyperpolarization-activated current (i(f)) in sino-atrial node myocytes.
1994,
Pubmed
Dick,
The effect of surface microvilli on the water permeability of single toad oocytes.
1970,
Pubmed
Dick,
The activities and concentrations of sodium and potassium in toad oocytes.
1969,
Pubmed
Frace,
Control of the hyperpolarization-activated cation current by external anions in rabbit sino-atrial node cells.
1992,
Pubmed
Gauss,
Molecular identification of a hyperpolarization-activated channel in sea urchin sperm.
1998,
Pubmed
Goethals,
Use-dependent block of the pacemaker current I(f) in rabbit sinoatrial node cells by zatebradine (UL-FS 49). On the mode of action of sinus node inhibitors.
1993,
Pubmed
Hartzell,
Calcium-activated chloride channels.
2005,
Pubmed
Henrikson,
Identification of a surface charged residue in the S3-S4 linker of the pacemaker (HCN) channel that influences activation gating.
2003,
Pubmed
,
Xenbase
Hescheler,
Does the organic calcium channel blocker D600 act from inside or outside on the cardiac cell membrane?
1982,
Pubmed
Hestrin,
The properties and function of inward rectification in rod photoreceptors of the tiger salamander.
1987,
Pubmed
Ho,
High selectivity of the i(f) channel to Na+ and K+ in rabbit isolated sinoatrial node cells.
1994,
Pubmed
Isenberg,
Isolated bovine ventricular myocytes. Characterization of the action potential.
1982,
Pubmed
Ishii,
Molecular characterization of the hyperpolarization-activated cation channel in rabbit heart sinoatrial node.
1999,
Pubmed
Jentsch,
Molecular structure and physiological function of chloride channels.
2002,
Pubmed
Kuruma,
A hyperpolarization- and acid-activated nonselective cation current in Xenopus oocytes.
2000,
Pubmed
,
Xenbase
Lesso,
Helical secondary structure of the external S3-S4 linker of pacemaker (HCN) channels revealed by site-dependent perturbations of activation phenotype.
2003,
Pubmed
Ludwig,
A family of hyperpolarization-activated mammalian cation channels.
1998,
Pubmed
Macri,
Structural elements of instantaneous and slow gating in hyperpolarization-activated cyclic nucleotide-gated channels.
2004,
Pubmed
Macri,
Separable gating mechanisms in a Mammalian pacemaker channel.
2002,
Pubmed
Maruoka,
Cation-dependent gating of the hyperpolarization-activated cation current in the rabbit sino-atrial node cells.
1994,
Pubmed
Miledi,
A calcium-dependent transient outward current in Xenopus laevis oocytes.
1982,
Pubmed
,
Xenbase
Miledi,
Chloride current induced by injection of calcium into Xenopus oocytes.
1984,
Pubmed
,
Xenbase
Moroni,
Kinetic and ionic properties of the human HCN2 pacemaker channel.
2000,
Pubmed
Pian,
Regulation of gating and rundown of HCN hyperpolarization-activated channels by exogenous and endogenous PIP2.
2006,
Pubmed
,
Xenbase
Pian,
Modulation of cyclic nucleotide-regulated HCN channels by PIP(2) and receptors coupled to phospholipase C.
2007,
Pubmed
,
Xenbase
Proenza,
Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels.
2002,
Pubmed
Proenza,
Distinct populations of HCN pacemaker channels produce voltage-dependent and voltage-independent currents.
2006,
Pubmed
Proenza,
Pacemaker channels produce an instantaneous current.
2002,
Pubmed
Qu,
MiRP1 modulates HCN2 channel expression and gating in cardiac myocytes.
2004,
Pubmed
Raes,
Use-dependent block of Ih in mouse dorsal root ganglion neurons by sinus node inhibitors.
1998,
Pubmed
Santoro,
Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain.
1998,
Pubmed
,
Xenbase
Schmieder,
Characterization of the putative chloride channel xClC-5 expressed in Xenopus laevis oocytes and comparison with endogenous chloride currents.
1998,
Pubmed
,
Xenbase
Sha,
Heterologous expression of the Na(+),K(+)-ATPase gamma subunit in Xenopus oocytes induces an endogenous, voltage-gated large diameter pore.
2001,
Pubmed
,
Xenbase
Stampe,
Unidirectional fluxes through ion channels expressed in Xenopus oocytes.
1998,
Pubmed
,
Xenbase
Stieber,
Bradycardic and proarrhythmic properties of sinus node inhibitors.
2006,
Pubmed
Thollon,
Use-dependent inhibition of hHCN4 by ivabradine and relationship with reduction in pacemaker activity.
2007,
Pubmed
Tzounopoulos,
Induction of endogenous channels by high levels of heterologous membrane proteins in Xenopus oocytes.
1995,
Pubmed
,
Xenbase
Ulens,
Gi- and Gs-coupled receptors up-regulate the cAMP cascade to modulate HCN2, but not HCN1 pacemaker channels.
2001,
Pubmed
,
Xenbase
Ulens,
Functional heteromerization of HCN1 and HCN2 pacemaker channels.
2001,
Pubmed
,
Xenbase
Van Bogaert,
Use-dependent blockade of cardiac pacemaker current (If) by cilobradine and zatebradine.
2003,
Pubmed
Van Bogaert,
Pharmacological influence of specific bradycardic agents on the pacemaker current of sheep cardiac Purkinje fibres. A comparison between three different molecules.
1987,
Pubmed
Van Bogaert,
Use- and frequency-dependent blockade by UL-FS 49 of the if pacemaker current in sheep cardiac Purkinje fibres.
1990,
Pubmed
Weber,
Ion currents of Xenopus laevis oocytes: state of the art.
1999,
Pubmed
,
Xenbase
Xue,
An external determinant in the S5-P linker of the pacemaker (HCN) channel identified by sulfhydryl modification.
2002,
Pubmed
Xue,
Dominant-negative suppression of HCN1- and HCN2-encoded pacemaker currents by an engineered HCN1 construct: insights into structure-function relationships and multimerization.
2002,
Pubmed
,
Xenbase
Yu,
MinK-related peptide 1: A beta subunit for the HCN ion channel subunit family enhances expression and speeds activation.
2001,
Pubmed
,
Xenbase