title: Age-dependent alterations of voltage-gated Na(+) channel isoforms in rat sinoatrial node.
abstract: Multiple isoforms of voltage-gated Na(+) channels (NaChs) have been identified in sinoatrial node (SAN) and contribute to a rapid intrinsic heart rate. However, their roles in aging remain unclear. Here, we sought to clarify whether the age-related expression of NaChs contributes to the impaired SAN function during aging. Blockade of the tetrodotoxin (TTX)-sensitive Na(+) current with nanomolar concentrations of TTX prolonged the cycle length (CL) in both the rat intact heart and SAN. The effect of nanomolar concentrations of TTX on SAN pacemaking was lessened in adulthood compared with that in youth. Interestingly, the pacemaking became more sensitive to TTX and TTX-induced sinus arrhythmias occurred more frequently in the senescent group. The presences of NaCh α subunit isoforms Nav1.1, Nav1.6 as well as β subunit isoforms Navβ1 and Navβ3 in SAN were confirmed by immunohistochemistry. Western blot revealed a declination of Nav1.1, Nav1.6, Navβ1 and Navβ3 proteins during aging. Furthermore, laser captured SAN cells were used for further real-time quantitative RT-PCR analysis, which also confirmed the presences of Nav1.1, Nav1.6, Navβ1 and Navβ3 mRNA and their reduced levels in rat SAN during aging. These results indicated an age-dependent alterations in expression and relative function of NaCh in rat SAN.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Ion Channel Disease Laboratory, Key Laboratory of Environment and Genes related to Diseases of Education Ministry, Xi'an, Shaanxi, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Ion Channel Disease Laboratory, Key Laboratory of Environment and Genes related to Diseases of Education Ministry, Xi'an, Shaanxi, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
authors.forename: Pei
authors.initials: P
authors.lastname: Yang
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Shienfong
authors.initials: S
authors.lastname: Lin
authors.affiliation: Cardiac Electrophysiology Research Laboratory Texas Heart Institute/St. Luke's Hospital, Advanced Cardiac Arrhythmia Center University of Texas School of Medicine at Houston, Houston, TX, USA.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Institute of Medical Electronics in Medical School, Key Laboratory of Biomedical Information Engineering, Ministry of Education, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Ion Channel Disease Laboratory, Key Laboratory of Environment and Genes related to Diseases of Education Ministry, Xi'an, Shaanxi, PR China. Electronic address: draiqunma@126.com.
authors.forename: Aiqun
authors.initials: A
authors.lastname: Ma
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D005786:Gene Expression Regulation; D008297:Male; D020033:Protein Isoforms / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012849:Sinoatrial Node; D061566:Voltage-Gated Sodium Channels / Q000096:biosynthesis*
chemical_list: D020033:Protein Isoforms; D061566:Voltage-Gated Sodium Channels
keywords: Aging; Automaticity; Optical mapping; Sinoatrial node; Sodium channel