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HCN Channels and Heart Rate  [PDF]
Pietro Scicchitano,Santa Carbonara,Gabriella Ricci,Cosimo Mandurino,Manuela Locorotondo,Gabriella Bulzis,Michele Gesualdo,Annapaola Zito,Rosa Carbonara,Ilaria Dentamaro,Graziano Riccioni,Marco Matteo Ciccone
Molecules , 2012, DOI: 10.3390/molecules17044225
Abstract: Hyperpolarization and Cyclic Nucleotide (HCN) -gated channels represent the molecular correlates of the “funny” pacemaker current (If), a current activated by hyperpolarization and considered able to influence the sinus node function in generating cardiac impulses. HCN channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. This channel family comprises four members: HCN1-4, but there is a general agreement to consider HCN4 as the main isoform able to control heart rate. This review aims to summarize advanced insights into the structure, function and cellular regulation of HCN channels in order to better understand the role of such channels in regulating heart rate and heart function in normal and pathological conditions. Therefore, we evaluated the possible therapeutic application of the selective HCN channels blockers in heart rate control.
白 三 叶 抗 旱 生 理 的 研 究  [PDF]
金忠民,沙 伟
北方园艺 , 2010, DOI: 10.11937/bfyy.201018019
Simple Organics and Biomonomers Identified in HCN Polymers: An Overview  [PDF]
Marta Ruiz-Bermejo,María-Paz Zorzano,Susana Osuna-Esteban
Life , 2013, DOI: 10.3390/life3030421
Abstract: Hydrogen cyanide (HCN) is a ubiquitous molecule in the Universe. It is a compound that is easily produced in significant yields in prebiotic simulation experiments using a reducing atmosphere. HCN can spontaneously polymerise under a wide set of experimental conditions. It has even been proposed that HCN polymers could be present in objects such as asteroids, moons, planets and, in particular, comets. Moreover, it has been suggested that these polymers could play an important role in the origin of life. In this review, the simple organics and biomonomers that have been detected in HCN polymers, the analytical techniques and procedures that have been used to detect and characterise these molecules and an exhaustive classification of the experimental/environmental conditions that favour the formation of HCN polymers are summarised. Nucleobases, amino acids, carboxylic acids, cofactor derivatives and other compounds have been identified in HCN polymers. The great molecular diversity found in HCN polymers encourages their placement at the central core of a plausible protobiological system.
HCN in the inner envelope of {chi} Cygni  [PDF]
Debiprosad Duari,Jennifer Hatchell
Physics , 2000,
Abstract: We have detected the (0,11c,0)J=3-2 and (0,0,0)J=8-7 transitions of HCN towards the S star {chi} Cygni. The excitation requirements of these transitions are too high to be satisfied in the outer envelope of the star, and the emission must originate within {solar}20 stellar radii, ie. the molecule must be forming close to the star. This conclusion is supported by a model for AGB stars in which molecules including HCN form in a shocked wind close to the stellar surface.
The interstellar gas-phase chemistry of HCN and HNC  [PDF]
Jean-Christophe Loison,Valentine Wakelam,Kevin M. Hickson
Physics , 2014, DOI: 10.1093/mnras/stu1089
Abstract: We review the reactions involving HCN and HNC in dark molecular clouds to elucidate new chemical sources and sinks of these isomers. We find that the most important reactions for the HCN-HNC system are Dissociative Recombination (DR) reactions of HCNH+ (HCNH+ + e-), the ionic CN + H3+, HCN + C+, HCN and HNC reactions with H+/He+/H3+/H3O+/HCO+, the N + CH2 reaction and two new reactions: H + CCN and C + HNC. We test the effect of the new rate constants and branching ratios on the predictions of gas-grain chemical models for dark cloud conditions. The rapid C + HNC reaction keeps the HCN/HNC ratio significantly above one as long as the carbon atom abundance remains high. However, the reaction of HCN with H3+ followed by DR of HCNH+ acts to isomerize HCN into HNC when carbon atoms and CO are depleted leading to a HCN/HNC ratio close to or slightly greater than 1. This agrees well with observations in TMC-1 and L134N taking into consideration the overestimation of HNC abundances through the use of the same rotational excitation rate constants for HNC as for HCN in many radiative transfer models.
The Role of HCN Channels on Membrane Excitability in the Nervous System  [PDF]
Daisuke Kase,Keiji Imoto
Journal of Signal Transduction , 2012, DOI: 10.1155/2012/619747
Abstract: Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels were first reported in heart cells and are recently known to be involved in a variety of neural functions in healthy and diseased brains. HCN channels generate inward currents when the membrane potential is hyperpolarized. Voltage dependence of HCN channels is regulated by intracellular signaling cascades, which contain cyclic AMP, PIP2, and TRIP8b. In addition, voltage-gated potassium channels have a strong influence on HCN channel activity. Because of these funny features, HCN channel currents, previously called funny currents, can have a wide range of functions that are determined by a delicate balance of modulatory factors. These multifaceted features also make it difficult to predict and elucidate the functional role of HCN channels in actual neurons. In this paper, we focus on the impacts of HCN channels on neural activity. The functions of HCN channels reported previously will be summarized, and their mechanisms will be explained by using numerical simulation of simplified model neurons. 1. Introduction Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels, first identified in 1976 in the heart by Noma and Irisawa [1] and characterized by Brown and Difrancesco [2] and Weiss and his colleague [3], are cation channels that open when the membrane potential is hyperpolarized. The general structure of HCN channels resembles that of the voltage-gated K+ channels. HCN channels consist of four subunits that have six transmembrane segments [4], the canonical GYG sequence in the pore forming region, and the positively charged S4 segment [4, 5]. But the K+ permeability of HCN channels is not so selective as typical K+ channels and is permeable to Na+ [6]. Thus a typical current reversal potential of HCN channels is around ?30?mV. For voltage-dependent gating, inward movement of S4 segment in response to hyperpolarization is reported [7–9], but molecular aspects of channel opening are still unknown. For example, HCN channels require extracellular Cl? and extracellular K+ to open [4]. Cyclic-AMP-(cAMP-) binding site locates near the C terminus, and cAMP affects the voltage dependence of activation in some HCN channel isoforms [10]. Phosphatidylinositol 4,5-bisphosphate (PIP2) is also known as a modulator of HCN channels; it shifts the voltage dependence through a different mechanism from that of cAMP [11, 12]. These multifaceted features endow HCN channels to work in many functions described below. In this paper, we try to understand the physiological significance of these
The HNC/HCN Ratio in Star-Forming Regions  [PDF]
Dawn Graninger,Eric Herbst,Karin I. Oberg,Anton I. Vasyunin
Physics , 2014, DOI: 10.1088/0004-637X/787/1/74
Abstract: HNC and HCN, typically used as dense gas tracers in molecular clouds, are a pair of isomers that have great potential as a temperature probe because of temperature dependent, isomer-specific formation and destruction pathways. Previous observations of the HNC/HCN abundance ratio show that the ratio decreases with increasing temperature, something that standard astrochemical models cannot reproduce. We have undertaken a detailed parameter study on which environmental characteristics and chemical reactions affect the HNC/HCN ratio and can thus contribute to the observed dependence. Using existing gas and gas-grain models updated with new reactions and reaction barriers, we find that in static models the H + HNC gas-phase reaction regulates the HNC/HCN ratio under all conditions, except for very early times. We quantitively constrain the combinations of H abundance and H + HNC reaction barrier that can explain the observed HNC/HCN temperature dependence and discuss the implications in light of new quantum chemical calculations. In warm-up models, gas-grain chemistry contributes significantly to the predicted HNC/HCN ratio and understanding the dynamics of star formation is therefore key to model the HNC/HCN system.
On the abundance of non-cometary HCN on Jupiter  [PDF]
Julianne I. Moses,Channon Visscher,Thomas C. Keane,Aubrey Sperier
Physics , 2010, DOI: 10.1039/c003954c
Abstract: Using one-dimensional thermochemical/photochemical kinetics and transport models, we examine the chemistry of nitrogen-bearing species in the Jovian troposphere in an attempt to explain the low observational upper limit for HCN. We track the dominant mechanisms for interconversion of N2-NH3 and HCN-NH3 in the deep, hightemperature troposphere and predict the rate-limiting step for the quenching of HCN at cooler tropospheric altitudes. Consistent with other investigations that were based solely on time-scale arguments, our models suggest that transport-induced quenching of thermochemically derived HCN leads to very small predicted mole fractions of hydrogen cyanide in Jupiter's upper troposphere. By the same token, photochemical production of HCN is ineffective in Jupiter's troposphere: CH4-NH3 coupling is inhibited by the physical separation of the CH4 photolysis region in the upper stratosphere from the NH3 photolysis and condensation region in the troposphere, and C2H2-NH3 coupling is inhibited by the low tropospheric abundance of C2H2. The upper limits from infrared and submillimeter observations can be used to place constraints on the production of HCN and other species from lightning and thundershock sources.
Processing of Retinal Signals in Normal and HCN Deficient Mice  [PDF]
Luca Della Santina,Ilaria Piano,Lorenzo Cangiano,Antonella Caputo,Andreas Ludwig,Luigi Cervetto,Claudia Gargini
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0029812
Abstract: This study investigates the role of two different HCN channel isoforms in the light response of the outer retina. Taking advantage of HCN-deficient mice models and of in vitro (patch-clamp) and in vivo (ERG) recordings of retinal activity we show that HCN1 and HCN2 channels are expressed at distinct retinal sites and serve different functions. Specifically, HCN1 operate mainly at the level of the photoreceptor inner segment from where, together with other voltage sensitive channels, they control the time course of the response to bright light. Conversely, HCN2 channels are mainly expressed on the dendrites of bipolar cells and affect the response to dim lights. Single cell recordings in HCN1?/? mice or during a pharmacological blockade of Ih show that, contrary to previous reports, Ikx alone is able to generate the fast initial transient in the rod bright flash response. Here we demonstrate that the relative contribution of Ih and Ikx to the rods' temporal tuning depends on the membrane potential. This is the first instance in which the light response of normal and HCN1- or HCN2-deficient mice is analyzed in single cells in retinal slice preparations and in integrated full field ERG responses from intact animals. This comparison reveals a high degree of correlation between single cell current clamp data and ERG measurements. A novel picture emerges showing that the temporal profile of the visual response to dim and bright luminance changes is separately determined by the coordinated gating of distinct voltage dependent conductances in photoreceptors and bipolar cells.
HCN Channels Are Not Required for Mechanotransduction in Sensory Hair Cells of the Mouse Inner Ear  [PDF]
Geoffrey C. Horwitz,Andrea Lelli,Gwena?lle S. G. Géléoc,Jeffrey R. Holt
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0008627
Abstract: The molecular composition of the hair cell transduction channel has not been identified. Here we explore the novel hypothesis that hair cell transduction channels include HCN subunits. The HCN family of ion channels includes four members, HCN1-4. They were orginally identified as the molecular correlates of the hyperpolarization-activated, cyclic nucleotide gated ion channels that carry currents known as If, IQ or Ih. However, based on recent evidence it has been suggested that HCN subunits may also be components of the elusive hair cell transduction channel. To investigate this hypothesis we examined expression of mRNA that encodes HCN1-4 in sensory epithelia of the mouse inner ear, immunolocalization of HCN subunits 1, 2 and 4, uptake of the transduction channel permeable dye, FM1-43 and electrophysiological measurement of mechanotransduction current. Dye uptake and transduction current were assayed in cochlear and vestibular hair cells of wildtype mice exposed to HCN channel blockers or a dominant-negative form of HCN2 that contained a pore mutation and in mutant mice that lacked HCN1, HCN2 or both. We found robust expression of HCNs 1, 2 and 4 but little evidence that localized HCN subunits in hair bundles, the site of mechanotransduction. Although high concentrations of the HCN antagonist, ZD7288, blocked 50–70% of the transduction current, we found no reduction of transduction current in either cochlear or vestibular hair cells of HCN1- or HCN2- deficient mice relative to wild-type mice. Furthermore, mice that lacked both HCN1 and HCN2 also had normal transduction currents. Lastly, we found that mice exposed to the dominant-negative mutant form of HCN2 had normal transduction currents as well. Taken together, the evidence suggests that HCN subunits are not required for mechanotransduction in hair cells of the mouse inner ear.
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