Age-associated expression of HCN channel isoforms in rat sinoatrial node.
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.
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.
Xin
X
Huang
Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710004, P.R. China.
Pei
P
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.
Zhao
Z
Yang
School of Electrical Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China.
Hong
H
Zhang
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.
Aiqun
A
Ma
D000367:Age Factors; D000818:Animals; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D008297:Male; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D017207:Rats, Sprague-Dawley; D012849:Sinoatrial Node / Q000201:enzymology*
D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D020033:Protein Isoforms
Aging; ion channels; sick sinus syndrome; sinoatrial node