HCN2 explained

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated ion channel 2 is a protein that in humans is encoded by the HCN2 gene.^{[1] [2] [3] [4]}

Interactions

HCN2 has been shown to interact with HCN1^{[5] [6]} and HCN4.^[5]

Function

The function of the channel is not known although its activation by hyperpolarization alludes to the funny channels in the sinoatrial node of the heart (which form the basis of spontaneous generation of electrical rhythm). These channels have recently been associated with chronic pain and blocking the gene is associated with resolution of neuropathic episodes of pain.^[7]

See also

• Cyclic nucleotide-gated ion channel

References

Further reading

• Kleiderlein JJ, Nisson PE, Jessee J, Li WB, Becker KG, Derby ML, Ross CA, Margolis RL . CCG repeats in cDNAs from human brain . Human Genetics . 103 . 6 . 666–73 . Dec 1998 . 9921901 . 10.1007/s004390050889 . 23696667 .
• Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F, Biel M . Two pacemaker channels from human heart with profoundly different activation kinetics . The EMBO Journal . 18 . 9 . 2323–9 . May 1999 . 10228147 . 1171315 . 10.1093/emboj/18.9.2323 .
• Vaccari T, Moroni A, Rocchi M, Gorza L, Bianchi ME, Beltrame M, DiFrancesco D . The human gene coding for HCN2, a pacemaker channel of the heart . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1446 . 3 . 419–25 . Sep 1999 . 10524219 . 10.1016/s0167-4781(99)00092-5 . 11577/134307 . free .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Research . 10 . 11 . 1788–95 . Nov 2000 . 11076863 . 310948 . 10.1101/gr.143000 .
• Ulens C, Tytgat J . Functional heteromerization of HCN1 and HCN2 pacemaker channels . The Journal of Biological Chemistry . 276 . 9 . 6069–72 . Mar 2001 . 11133998 . 10.1074/jbc.C000738200 . free .
• Proenza C, Tran N, Angoli D, Zahynacz K, Balcar P, Accili EA . Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels . The Journal of Biological Chemistry . 277 . 33 . 29634–42 . Aug 2002 . 12034718 . 10.1074/jbc.M200504200 . free .
• Qu J, Altomare C, Bucchi A, DiFrancesco D, Robinson RB . Functional comparison of HCN isoforms expressed in ventricular and HEK 293 cells . Pflügers Archiv . 444 . 5 . 597–601 . Aug 2002 . 12194012 . 10.1007/s00424-002-0860-7 . 508732 .
• Sesti F, Rajan S, Gonzalez-Colaso R, Nikolaeva N, Goldstein SA . Hyperpolarization moves S4 sensors inward to open MVP, a methanococcal voltage-gated potassium channel . Nature Neuroscience . 6 . 4 . 353–61 . Apr 2003 . 12640457 . 10.1038/nn1028 . 22130861 .
• Stieber J, Thomer A, Much B, Schneider A, Biel M, Hofmann F . Molecular basis for the different activation kinetics of the pacemaker channels HCN2 and HCN4 . The Journal of Biological Chemistry . 278 . 36 . 33672–80 . Sep 2003 . 12813043 . 10.1074/jbc.M305318200 . free .
• Bender RA, Soleymani SV, Brewster AL, Nguyen ST, Beck H, Mathern GW, Baram TZ . Enhanced expression of a specific hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN) in surviving dentate gyrus granule cells of human and experimental epileptic hippocampus . The Journal of Neuroscience . 23 . 17 . 6826–36 . Jul 2003 . 12890777 . 10.1523/JNEUROSCI.23-17-06826.2003. 3100807 .
• Much B, Wahl-Schott C, Zong X, Schneider A, Baumann L, Moosmang S, Ludwig A, Biel M . Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels . The Journal of Biological Chemistry . 278 . 44 . 43781–6 . Oct 2003 . 12928435 . 10.1074/jbc.M306958200 . free .
• Michels G, Er F, Khan I, Südkamp M, Herzig S, Hoppe UC . Single-channel properties support a potential contribution of hyperpolarization-activated cyclic nucleotide-gated channels and If to cardiac arrhythmias . Circulation . 111 . 4 . 399–404 . Feb 2005 . 15687126 . 10.1161/01.CIR.0000153799.65783.3A . free .
• Akhavan A, Atanasiu R, Noguchi T, Han W, Holder N, Shrier A . Identification of the cyclic-nucleotide-binding domain as a conserved determinant of ion-channel cell-surface localization . Journal of Cell Science . 118 . Pt 13 . 2803–12 . Jul 2005 . 15961404 . 10.1242/jcs.02423 . free .
• Calloe K, Elmedyb P, Olesen SP, Jorgensen NK, Grunnet M . Hypoosmotic cell swelling as a novel mechanism for modulation of cloned HCN2 channels . Biophysical Journal . 89 . 3 . 2159–69 . Sep 2005 . 15980171 . 1366717 . 10.1529/biophysj.105.063792 . 2005BpJ....89.2159C .

Notes and References

1. Santoro B, Grant SG, Bartsch D, Kandel ER . Interactive cloning with the SH3 domain of N-src identifies a new brain specific ion channel protein, with homology to eag and cyclic nucleotide-gated channels . Proceedings of the National Academy of Sciences of the United States of America . 94 . 26 . 14815–20 . Dec 1997 . 9405696 . 25120 . 10.1073/pnas.94.26.14815 . 1997PNAS...9414815S . free .
2. Santoro B, Liu DT, Yao H, Bartsch D, Kandel ER, Siegelbaum SA, Tibbs GR . Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain . Cell . 93 . 5 . 717–29 . May 1998 . 9630217 . 10.1016/S0092-8674(00)81434-8 . 10265917 . free .
3. Hofmann F, Biel M, Kaupp UB . International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels . Pharmacological Reviews . 57 . 4 . 455–62 . Dec 2005 . 16382102 . 10.1124/pr.57.4.8 . 45853869 .
4. Web site: Entrez Gene: HCN2 hyperpolarization activated cyclic nucleotide-gated potassium channel 2.
5. Much B, Wahl-Schott C, Zong X, Schneider A, Baumann L, Moosmang S, Ludwig A, Biel M . Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels . The Journal of Biological Chemistry . 278 . 44 . 43781–6 . Oct 2003 . 12928435 . 10.1074/jbc.M306958200 . free .
6. Proenza C, Tran N, Angoli D, Zahynacz K, Balcar P, Accili EA . Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels . The Journal of Biological Chemistry . 277 . 33 . 29634–42 . Aug 2002 . 12034718 . 10.1074/jbc.M200504200 . free .
7. News: Gene find may lead to pills that kill chronic pain . https://web.archive.org/web/20121106114758/http://articles.timesofindia.indiatimes.com/2011-09-10/science/30138741_1_chronic-pain-neuropathic-pain-gene . dead . 6 November 2012 . . 10 September 2011.