Faculty Opinions recommendation of Forebrain HCN1 channels contribute to hypnotic actions of ketamine.

2014 ◽  
Author(s):  
Peter Nagele
Keyword(s):  
Hcn1 Channels

scholarly journals Presynaptic HCN1 channels regulate CaV3.2 activity and neurotransmission at select cortical synapses

2011 ◽  
Vol 14 (4) ◽  
pp. 478-486 ◽  
Author(s):  
Zhuo Huang ◽  
Rafael Lujan ◽  
Ivan Kadurin ◽  
Victor N Uebele ◽  
John J Renger ◽  
...  
Keyword(s):  
Cortical Synapses ◽  
Hcn1 Channels

Role of Ih in the firing pattern of mammalian cold thermoreceptor endings

2012 ◽  
Vol 108 (11) ◽  
pp. 3009-3023 ◽  
Author(s):  
Patricio Orio ◽  
Andrés Parra ◽  
Rodolfo Madrid ◽  
Omar González ◽  
Carlos Belmonte ◽  
...  
Keyword(s):  
Skin Temperature ◽  
Neural Coding ◽  
Firing Pattern ◽  
Firing Frequency ◽  
Sensory Transduction ◽  
Nerve Endings ◽  
Subthreshold Resonance ◽  
Cold Sensitive ◽  
Hcn1 Channels

Mammalian peripheral cold thermoreceptors respond to cooling of their sensory endings with an increase in firing rate and modification of their discharge pattern. We recently showed that cultured trigeminal cold-sensitive (CS) neurons express a prominent hyperpolarization-activated current ( Ih), mainly carried by HCN1 channels, supporting subthreshold resonance in the soma without participating in the response to acute cooling. However, peripheral pharmacological blockade of Ih, or characterization of HCN1−/− mice, reveals a deficit in acute cold detection. Here we investigated the role of Ih in CS nerve endings, where cold sensory transduction actually takes place. Corneal CS nerve endings in mice show a rhythmic spiking activity at neutral skin temperature that switches to bursting mode when the temperature is lowered. Ih blockers ZD7288 and ivabradine alter firing patterns of CS nerve endings, lengthening interspike intervals and inducing bursts at neutral skin temperature. We characterized the CS nerve endings from HCN1−/− mouse corneas and found that they behave similar to wild type, although with a lower slope in the firing frequency vs. temperature relationship, thus explaining the deficit in cold perception of HCN1−/− mice. The firing pattern of nerve endings from HCN1−/− mice was also affected by ZD7288, which we attribute to the presence of HCN2 channels in the place of HCN1. Mathematical modeling shows that the firing phenotype of CS nerve endings from HCN1−/− mice can be reproduced by replacing HCN1 channels with the slower HCN2 channels rather than by abolishing Ih. We propose that Ih carried by HCN1 channels helps tune the frequency of the oscillation and the length of bursts underlying regular spiking in cold thermoreceptors, having important implications for neural coding of cold sensation.

scholarly journals A Possible Link Between HCN Channels and Depression

2018 ◽  
Vol 2 ◽  
pp. 247054701878778 ◽  
Author(s):  
Chung Sub Kim ◽  
Daniel Johnston
Keyword(s):  
Protein Expression ◽  
Neuronal Excitability ◽  
Acute Stress ◽  
Hcn Channels ◽  
Chronic Unpredictable Stress ◽  
Ca1 Neurons ◽  
Ca1 Region ◽  
Hcn1 Channels ◽  
The Brain

Growing evidence suggests a possible link between hyperpolarization-activated cyclic nucleotide-gated nonselective cation (HCN) channels and depression. In a recent study published in Molecular Psychiatry, we first demonstrate that Ih (the membrane current mediated by HCN channels) and HCN1 protein expression were increased in dorsal, but not in ventral, CA1 region following chronic, but not acute stress. This upregulation of Ih was restricted to the perisomatic region of CA1 neurons and contributed to a reduction of neuronal excitability. A reduction of HCN1 protein expression in dorsal CA1 region before the onset of chronic unpredictable stress-induced depression was sufficient to provide resilient effects to chronic unpredictable stress. Furthermore, in vivo block of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) pumps, a manipulation known to increase intracellular calcium levels and upregulate Ih, produced anxiogenic-like behavior and an increase in Ih, similar to that observed in chronic unpredictable stress model of depression. Here, we share our view on (1) how the function and expression of HCN1 channels are changed in the brain in a subcellular region-specific manner during the development of depression and (2) how a reduction of HCN1 protein expression provides resilience to chronic stress.

scholarly journals Intracellular Mg2+ is a voltage-dependent pore blocker of HCN channels

2008 ◽  
Vol 295 (2) ◽  
pp. C557-C565 ◽  
Author(s):  
Sriharsha Vemana ◽  
Shilpi Pandey ◽  
H. Peter Larsson
Keyword(s):  
Binding Site ◽  
Physiological Role ◽  
Time Dependent ◽  
Inward Rectification ◽  
Hcn Channels ◽  
Membrane Hyperpolarization ◽  
Outward Currents ◽  
Voltage Dependent ◽  
Hcn1 Channels ◽  
Pore Blocker

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization that creates time-dependent, inward rectifying currents, gated by the movement of the intrinsic voltage sensor S4. However, inward rectification of the HCN currents is not only observed in the time-dependent HCN currents, but also in the instantaneous HCN tail currents. Inward rectification can also be seen in mutant HCN channels that have mainly time-independent currents ( 5 ). In the present study, we show that intracellular Mg2+ functions as a voltage-dependent blocker of HCN channels, acting to reduce the outward currents. The affinity of HCN channels for Mg2+ is in the physiological range, with Mg2+ binding with an IC50 of 0.53 mM in HCN2 channels and 0.82 mM in HCN1 channels at +50 mV. The effective electrical distance for the Mg2+ binding site was found to be 0.19 for HCN1 channels, suggesting that the binding site is in the pore. Removing a cysteine in the selectivity filter of HCN1 channels reduced the affinity for Mg2+, suggesting that this residue forms part of the binding site deep within the pore. Our results suggest that Mg2+ acts as a voltage-dependent pore blocker and, therefore, reduces outward currents through HCN channels. The pore-blocking action of Mg2+ may play an important physiological role, especially for the slowly gating HCN2 and HCN4 channels. Mg2+ could potentially block outward hyperpolarizing HCN currents at the plateau of action potentials, thus preventing a premature termination of the action potential.

scholarly journals Hysteresis in the Voltage Dependence of HCN Channels

2005 ◽  
Vol 125 (3) ◽  
pp. 305-326 ◽  
Author(s):  
Roope Männikkö ◽  
Shilpi Pandey ◽  
H. Peter Larsson ◽  
Fredrik Elinder
Keyword(s):  
Voltage Dependence ◽  
Rhythmic Activity ◽  
Ionic Currents ◽  
Hcn Channels ◽  
Molecular Conformations ◽  
Gating Charge ◽  
Voltage Curve ◽  
Current Change ◽  
Voltage Hysteresis ◽  
Hcn1 Channels

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) ion channels are important for rhythmic activity in the brain and in the heart. In this study, using ionic and gating current measurements, we show that cloned spHCN channels undergo a hysteresis in their voltage dependence during normal gating. For example, both the gating charge versus voltage curve, Q(V), and the conductance versus voltage curve, G(V), are shifted by about +60 mV when measured from a hyperpolarized holding potential compared with a depolarized holding potential. In addition, the kinetics of the tail current and the activation current change in parallel to the voltage shifts of the Q(V) and G(V) curves. Mammalian HCN1 channels display similar effects in their ionic currents, suggesting that the mammalian HCN channels also undergo voltage hysteresis. We propose a model in which HCN channels transit between two modes. The voltage dependence in the two modes is shifted relative to each other, and the occupancy of the two modes depends on the previous activation of the channel. The shifts in the voltage dependence are fast (τ ≈ 100 ms) and are not accompanied by any apparent inactivation. In HCN1 channels, the shift in voltage dependence is slower in a 100 mM K extracellular solution compared with a 1 mM K solution. Based on these findings, we suggest that molecular conformations similar to slow (C-type) inactivation of K channels underlie voltage hysteresis in HCN channels. The voltage hysteresis results in HCN channels displaying different voltage dependences during different phases in the pacemaker cycle. Computer simulations suggest that voltage hysteresis in HCN channels decreases the risk of arrhythmia in pacemaker cells.

Sign in / Sign up

Export Citation Format

Share Document