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Experimental biology and medicine (Maywood, N.J.)
Feb, 2016;241 (3): 331-9.

Age-associated expression of HCN channel isoforms in rat sinoatrial node.

Xin Huang, Pei Yang, Zhao Yang, Hong Zhang, Aiqun Ma
Author Information
  1. Xin Huang: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Ion Channel Disease Laboratory, Key Laboratory of Environment and Genes related to Diseases of Education Ministry, Xi'an, Shaanxi 710061, P.R. China.
  2. Pei Yang: Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710004, P.R. China.
  3. Zhao Yang: Institute of Medical Electronics in Medical School, Key Laboratory of Biomedical Information Engineering, Ministry of Education, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
  4. Hong Zhang: School of Electrical Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China.
  5. Aiqun Ma: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Ion Channel Disease Laboratory, Key Laboratory of Environment and Genes related to Diseases of Education Ministry, Xi'an, Shaanxi 710061, P.R. China drmaaiqun@163.com.
PMID: 26341471 DOI: 10.1177/1535370215603515

Abstract

The expression of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel isoforms varies among species, cardiac tissues, developmental stages, and disease generation. However, alterations in the HCN channels during aging remain unclear. We investigated the protein expressions of HCN channel isoforms, HCN1-HCN4, in the sinoatrial nodes (SANs) from young (1-month-old), adult (4-month-old), and aged (30-month-old) rats. We found that HCN2 and HCN4 proteins were present in rat SAN using immunohistochemistry; therefore, we quantitatively analyzed their expression by Western blot. Aim to correlate protein expression and pacemaking function, specific blockade of HCN channels with 3 µmol/L ivabradine prolonged the cycle length in the intact rat heart. During the senescent process, the HCN2 and HCN4 protein levels declined, which was accompanied with a decreased effect of ivabradine on rat SAN automaticity. These results indicated the age-associated expression and relative function of HCN channel isoforms.

Keywords

Aging ion channels sick sinus syndrome sinoatrial node

References

  1. Trends Cardiovasc Med. 2002 Jul;12(5):206-12 [PMID: 12161074]
  2. Circulation. 2007 Apr 10;115(14):1921-32 [PMID: 17420362]
  3. Circ Res. 2006 Dec 8;99(12):1384-93 [PMID: 17082478]
  4. Circulation. 2013 Dec 17;128(24):2585-94 [PMID: 24218458]
  5. Cancer Lett. 2014 Jan 1;342(1):104-12 [PMID: 24007862]
  6. Am J Physiol. 1992 Jan;262(1 Pt 2):H97-105 [PMID: 1733327]
  7. Drug Des Devel Ther. 2014 Jun 03;8:689-700 [PMID: 24940047]
  8. Basic Res Cardiol. 2007 Sep;102(5):429-35 [PMID: 17572839]
  9. Circ Res. 2001 Jul 6;89(1):E8-14 [PMID: 11440985]
  10. J Am Geriatr Soc. 1999 Sep;47(9):1125-35 [PMID: 10484258]
  11. Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15235-40 [PMID: 14657344]
  12. Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3507-12 [PMID: 12631690]
  13. Annu Rev Physiol. 1993;55:455-72 [PMID: 7682045]
  14. Eur J Biochem. 2001 Mar;268(6):1646-52 [PMID: 11248683]
  15. FASEB J. 2003 Sep;17(12):1592-608 [PMID: 12958166]
  16. Circ Res. 2011 Oct 14;109(9):1015-23 [PMID: 21903939]
  17. J Physiol. 2013 Sep 1;591(17):4117-24 [PMID: 23507880]
  18. N Engl J Med. 2006 Jan 12;354(2):151-7 [PMID: 16407510]
  19. J Cardiovasc Electrophysiol. 2003 Jan;14(1):104-6 [PMID: 12625620]
  20. Circ Res. 1999 Jul 9;85(1):e1-6 [PMID: 10400919]
  21. Nature. 1998 Jun 11;393(6685):587-91 [PMID: 9634236]
  22. Trends Cardiovasc Med. 2004 Jan;14(1):23-8 [PMID: 14720471]
  23. Basic Res Cardiol. 2009 Nov;104(6):621-9 [PMID: 19421833]
  24. Circulation. 1977 Jul;56(1):43-50 [PMID: 862170]
  25. Eur Heart J. 1993 Sep;14(9):1278-88 [PMID: 8223742]
  26. Circ Res. 2001 Mar 16;88(5):536-42 [PMID: 11249878]
  27. Br J Pharmacol. 1996 Jun;118(4):1051-7 [PMID: 8799581]
  28. Annu Rev Physiol. 2001;63:235-57 [PMID: 11181956]
  29. Neuron. 1998 Jul;21(1):5-7 [PMID: 9697846]
  30. Eur J Pharmacol. 1998 Jul 10;352(2-3):247-55 [PMID: 9716361]
  31. Curr Opin Pharmacol. 2014 Apr;15:83-90 [PMID: 24441197]
  32. J Physiol. 2003 Dec 1;553(Pt 2):395-405 [PMID: 14514868]
  33. Annu Rev Physiol. 2003;65:453-80 [PMID: 12471170]
  34. Circulation. 1973 Jan;47(1):86-93 [PMID: 4686607]
  35. Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1705-10 [PMID: 21220308]
  36. J Clin Invest. 2003 May;111(10):1537-45 [PMID: 12750403]
  37. Cardiovasc Res. 2005 Jun 1;66(3):472-81 [PMID: 15914112]
  38. EMBO J. 2003 Jan 15;22(2):216-24 [PMID: 12514127]

MeSH Term

Age Factors
Animals
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Male
Protein Isoforms
Rats, Sprague-Dawley
Sinoatrial Node

Chemicals

Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Protein Isoforms
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

Created with Highcharts 10.0.0HCNexpressionchannelisoformsratchannelsproteinsinoatrialHCN2HCN4SANfunctionivabradinenodehyperpolarization-activatedcyclicnucleotide-gatedcationvariesamongspeciescardiactissuesdevelopmentalstagesdiseasegenerationHoweveralterationsagingremainunclearinvestigatedexpressionsHCN1-HCN4nodesSANsyoung1-month-oldadult4-month-oldaged30-month-oldratsfoundproteinspresentusingimmunohistochemistrythereforequantitativelyanalyzedWesternblotAimcorrelatepacemakingspecificblockade3 µmol/Lprolongedcyclelengthintactheartsenescentprocesslevelsdeclinedaccompanieddecreasedeffectautomaticityresultsindicatedage-associatedrelativeAge-associatedAgingionsicksinussyndrome

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