title: Aging-associated changes in L-type calcium channels in the left atria of dogs.
abstract: Action potential (AP) contours vary considerably between the fibers of normal adult and aged left atria. The underlying ionic and molecular mechanisms that mediate these differences remain unknown. The aim of the present study was to investigate whether the L-type calcium current (ICa.L) and the L-type Ca2+channel of the left atria may be altered with age to contribute to atrial fibrillation (AF). Two groups of mongrel dogs (normal adults, 2-2.5 years old and older dogs, >8 years old) were used in this study. The inducibility of AF was quantitated using the cumulative window of vulnerability (WOV). A whole-cell patch-clamp was used to record APs and ICa.Lin left atrial (LA) cells obtained from the two groups of dogs. Protein and mRNA expression levels of the a1C (Cav1.2) subunit of the L-type calcium channel were assessed using western blotting and quantitative PCR (qPCR), respectively. Although the resting potential, AP amplitude and did not differ with age, the plateau potential was more negative and the APD90was longer in the aged cells compared with that in normal adult cells. Aged LA cells exhibited lower peak ICa.Lcurrent densities than normal adult LA cells (P<0.05). In addition, the Cav1.2 mRNA and protein expression levels in LA cells were decreased in the aged group compared with those in the normal adult group. The lower AP plateau potential and the decreased ICa.Lof LA cells in aged dogs may contribute to the slow and discontinuous conduction of the left atria. Furthermore, the reduction of the expression levels of Cav1.2 with age may be the molecular mechanism that mediates the decline in ICa.Lwith increasing age.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830011;
authors.forename: Tian-Yi
authors.initials: TY
authors.lastname: Gan
authors.forename: Weiwei
authors.initials: W
authors.lastname: Qiao
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Xu
authors.forename: Xian-Hui
authors.initials: XH
authors.lastname: Zhou
authors.forename: Bao-Peng
authors.initials: BP
authors.lastname: Tang
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Song
authors.forename: Yao-Dong
authors.initials: YD
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Fa-Peng
authors.initials: FP
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Mao
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
keywords: aging; atria; calcuim channel; cellular electrophysiology