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HCN (hyperpolarization-activated, cyclic nucleotide-gated) channels are members of the cyclic nucleotide-regulated channel family along with cyclic nucleotide-gated (CNG) channels. They are cationic channels that open under hyperpolarization.
|Cat No||Product Name / Activity|
|Inhibits the pacemaker current (If); also potassium channels blocker|
|Inhibits pacemaker (If) current and K+ outward currents.|
|Blocks hyperpolarization-activated current (If)|
|Inhibits pacemaker (If) current|
HCN (hyperpolarization-activated, cyclic nucleotide-gated) channels are members of the cyclic nucleotide-regulated channel family along with cyclic nucleotide-gated (CNG) channels. Each channel is made up of four subunits, with each subunit comprising six transmembrane α-helical segments, with the S4 segment thought to be the voltage sensor. They are cation permeable channels that open under hyperpolarization. In contrast to most voltage-gated ion channels, they are constitutively open at voltages near the resting membrane potential, so influence neuronal excitability, synaptic potential integration and neurotransmitter release. They are also gated by cyclic nucleotides, cAMP and cGMP, which enhance channel activity. There are four HCN isoforms, HCN1, 2, 3 and 4, which vary in their biophysical properties and in their expression levels across the heart and central nervous system; HCN1 is the fastest activating, while HCN4 is the slowest activating form. The C-terminus of the channel contains a cyclic-nucleotide binding domain where cyclic nucleotides confer their regulation.
The HCN channel current (Ih or If) is found in neurons, cardiac pacemaker cells and photoreceptors. In cardiac pacemaker cells the (If) current is known to control heart rate. HCN4 is the major isoform found in the adult sinoatrial node and in humans HCN4 mutations are associated with idiopathic sinus bradycardia and arrhythmias. In neurons HCN channels set the resting potential and contribute to neuronal pacemaking. Ih is activated following the end of the action potential and depolarizes the cell to initiate the next action potential. They contribute to mechanisms of epilepsy and pain.
Peripheral sensitization is the reduction in the threshold of excitability of sensory neurons that results in an augmented response to a given external stimulus. This poster outlines the excitatory and inhibitory signaling pathways involved in modulation of peripheral sensitization. The role of ion channels, GPCRs, neurotrophins, and cytokines in sensory neurons are also described.
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