Hyperpolarization-activated cyclic nucleotide–gated (HCN) channels are integral membrane proteins that serve as nonselective voltage-gated cation channels in the plasma membranes of heart and brain cells. HCN channels are sometimes referred to as pacemaker channels because they help to generate rhythmic activity within groups of heart and brain cells. HCN channels are activated by membrane hyperpolarization, are permeable to Na and K , and are constitutively open at voltages near the resting membrane potential. HCN channels are encoded by four genes ( HCN1 , 2 , 3 , 4 ) and are widely expressed throughout the heart and the central nervous system .
13-701: HCN may refer to: Science and mathematics [ edit ] HCN channel , a cellular ion channel Highly composite number , a type of integer Hydrogen cyanide , The toxic gas HCN Transportation [ edit ] Halcyonair , a Cape Verdean airline Headcorn railway station , in England Hengchun Airport , in Taiwan Other [ edit ] Health Communication Network , an Australian software company High Country News , an American newspaper Topics referred to by
26-454: A structural domain of about 120 residues. The best studied of these proteins is the prokaryotic catabolite gene activator (also known as the cAMP receptor protein ) (gene crp) where such a domain is known to be composed of three alpha-helices and a distinctive eight-stranded, antiparallel beta-barrel structure. There are six invariant amino acids in this domain, three of which are glycine residues that are thought to be essential for maintenance of
39-581: Is different from Wikidata All article disambiguation pages All disambiguation pages HCN channel The current through HCN channels, designated I f or I h , plays a key role in the control of cardiac and neuronal rhythmicity and is called the pacemaker current or "funny" current. Expression of single isoforms in heterologous systems such as human embryonic kidney ( HEK ) cells, Chinese hamster ovary ( CHO ) cells and Xenopus oocytes yield homotetrameric channels able to generate ion currents with properties similar to those of
52-492: Is evidence that HCN channels play roles in epilepsy and neuropathic pain . HCN channels have been shown to be important for activity-dependent mechanisms for olfactory sensory neuron growth. HCN1 and 2 channels have been found in dorsal root ganglia , basal ganglia , and the dendrites of neurons in the hippocampus . It has been found that human cortical neurons have particularly high amount of HCN1 channel expression in all layers. HCN channel trafficking along dendrites in
65-609: The GYG triplet signature of K -permeable channels, and a cyclic nucleotide-binding domain (CNBD) in the C-terminus. HCN isoforms are highly conserved in their core transmembrane regions and cyclic nucleotide binding domain (80–90% identical), but diverge in their amino- and carboxy-terminal cytoplasmic regions. HCN channels are regulated by both intracellular and extracellular molecules , but most importantly, by cyclic nucleotides (cAMP, cGMP, cCMP). Binding of cyclic nucleotides lowers
78-1051: The complex nature of HCN channel regulation, as well as the complex interactions between multiple ion channels, HCN channels are fine-tuned to respond to certain thresholds and agonists. This complexity is believed to affect neural plasticity . HCN channel was first identified in 1976 in the heart by Noma and Irisawa and characterized by Brown, Difrancesco and Weiss Cyclic nucleotide-binding domain 1kmu R:154-243 1cx4 A:170-259 1rl3 A:153-238 1ne6 A:153-238 1ne4 A:153-238 1rgs :153-238 1apk :153-238 1pvk A:153-238 1u7e B:153-238 2bpk :275-372 1bpk :271-362 1q43 A:535-620 1q5o A:535-620 1q3e A:535-620 1vp6 C:253-336 1u12 B:253-336 1i6x A:21-112 1hw5 A:21-112 1j59 B:21-112 1o3s A:21-112 1g6n B:21-112 1lb2 A:21-112 1cgp B:21-112 1ruo B:21-112 2cgp A:21-112 1o3r A:21-112 1i5z B:21-112 1o3t A:21-112 1run A:21-112 1o3q A:21-112 Proteins that bind cyclic nucleotides ( cAMP or cGMP ) share
91-494: The hippocampus of rats has shown that HCN channels are quickly shuttled to the surface in response to neural activity. HCN channels have also been observed in the retrotrapezoid nucleus (RTN), a respiratory control center that responds to chemical signals such as CO 2 . When HCN is inhibited, serotonin fails to stimulate chemoreceptors in the RTN. This illustrates a connection between HCN channels and respiratory regulation . Due to
104-518: The native I f / I h current, but with quantitative differences in the voltage-dependence, activation/deactivation kinetics and sensitivity to the nucleotide cyclic AMP (cAMP): HCN1 channels have a more positive threshold for activation, faster activation kinetics, and a lower sensitivity to cAMP, while HCN4 channels are slowly gating and strongly sensitive to cAMP. HCN2 and HCN3 have intermediate properties. Hyperpolarization -activated and cyclic nucleotide–gated (HCN) channels belong to
117-403: The same term [REDACTED] This disambiguation page lists articles associated with the title HCN . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=HCN&oldid=1223991383 " Category : Disambiguation pages Hidden categories: Short description
130-523: The spontaneous depolarization in pacemaker action potentials in the heart. HCN4 isoforms are regulated by cCMP and cAMP and these molecules are agonists at I f . All four HCN subunits are expressed in the brain. In addition to their proposed roles in pacemaking rhythmic or oscillatory activity, HCN channels may control the way that neurons respond to synaptic input. Initial studies suggest roles for HCN channels in sour taste, coordinated motor behavior and aspects of learning and memory. Clinically, there
143-546: The structural integrity of the beta-barrel. cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) contain two tandem copies of the cyclic nucleotide-binding domain. The cAPK's are composed of two different subunits, a catalytic chain and a regulatory chain, which contains both copies of the domain. The cGPK's are single chain enzymes that include the two copies of the domain in their N-terminal section. Vertebrate cyclic nucleotide-gated ion-channels also contain this domain. Two such cations channels have been fully characterized, one
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#1732773152062156-412: The superfamily of voltage-gated K (Kv) and cyclic nucleotide–gated (CNG) channels. HCN channels are thought to consist of four either identical or non-identical subunits that are integrally embedded in the cell membrane to create an ion-conducting pore. Each subunit comprises six membrane-spanning (S1–6) domains which include a putative voltage sensor (S4) and a pore region between S5 and S6 carrying
169-481: The threshold potential of HCN channels, thus activating them. cAMP is a primary agonist of HCN2 while cGMP and cCMP may also bind to it. All three, however, are potent agonists. HCN4 is the main isoform expressed in the sinoatrial node , but low levels of HCN1 and HCN2 have also been reported. The current through HCN channels, called the pacemaker current ( I f ), plays a key role in the generation and modulation of cardiac rhythmicity , as they are responsible for
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