Alterations in the expression of atrial calpains in electrical and structural remodeling during aging and atrial fibrillation

Xu,Guo-Jun; Gan,Tian-Yi; Tang,Bao-Peng; Chen,Zu-Heng; Mahemuti,Ailiman; Jiang,Tao; Song,Jian-Guo; Guo,Xia; Li,Yao-Dong; Zhou,Xian-Hui; Zhang,Yu; Li,Jin-Xin

doi:10.3892/mmr.2013.1684

Alterations in the expression of atrial calpains in electrical and structural remodeling during aging and atrial fibrillation

Authors:
- Guo-Jun Xu
- Tian-Yi Gan
- Bao-Peng Tang
- Zu-Heng Chen
- Ailiman Mahemuti
- Tao Jiang
- Jian-Guo Song
- Xia Guo
- Yao-Dong Li
- Xian-Hui Zhou
- Yu Zhang
- Jin-Xin Li
View Affiliations

Affiliations: Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China, Department of Animal Experiment, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China, Laboratory of Electrophysiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China, Department of Molecular Biology, Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China
Published online on: September 13, 2013 https://doi.org/10.3892/mmr.2013.1684
Pages: 1343-1352

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of this study was to investigate the correlation between the change in the expression of atrial calpains and electrical, molecular and structural remodeling during aging and atrial fibrillation (AF). Adult and aged canines in sinus rhythm (SR) and with persistent AF (induced by rapid atrial pacing) were investigated. A whole-cell patch clamp was used to measure the L‑type Ca2+ current (ICa-L) in cells in the left atrium. The mRNA and protein expression of the L‑type calcium channel alc subunit (LVDCCa1c) and calpains were measured by quantitative (q)PCR and western blot analysis. Histopathological and ultrastructural changes were analyzed via light and electron microscopy. The quantity of apoptotic myocytes was determined by a terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling (TUNEL) assay. In SR groups, atrial cells of the aged canines exhibited a longer action potential (AP) duration to 90% repolarization (APD90), lower AP plateau potential and peak ICa-L current densities (P<0.05). In the adult and aged groups, AF led to a higher maximum diastolic potential, an increase in AP amplitude and decreases in APD90, AP plateau potential and peak ICa-L densities (P<0.05). Compared with the control group, the mRNA and protein expression levels of LVDCCa1c were decreased in the aged groups; however, the mRNA and protein expression of calpain 1 was increased in the adult and the aged groups with AF (P<0.05). Samples of atrial tissue exhibited abnormal histopathological and ultrastructural changes, such as accelerated fibrosis and apoptosis with aging and in AF. Age‑related alterations in atrial tissues were attributed to the increased expression of calpain 1. The general pathophysiological alterations in normal aged atria may therefore produce a substrate that is conducive to AF.

View Figures

View References

1	Nattel S: New ideas about atrial fibrillation 50 years on. Nature. 415:219–226. 2002.PubMed/NCBI
2	Chen LY and Shen WK: Epidemiology of atrial fibrillation: a current perspective. Heart Rhythm. 4(Suppl 3): S1–S6. 2007. View Article : Google Scholar : PubMed/NCBI
3	Dun W, Yagi T, Rosen MR and Boyden PA: Calcium and potassium currents in cells from adult and aged canine right atria. Cardiovasc Res. 58:526–534. 2003. View Article : Google Scholar : PubMed/NCBI
4	Anyukhovsky EP, Sosunov EA, Plotnikov A, et al: Cellular electrophysiologic properties of old canine atria provide a substrate for arrhythmogenesis. Cardiovasc Res. 54:462–469. 2002. View Article : Google Scholar : PubMed/NCBI
5	Anyukhovsky EP, Sosunov EA, Chandra P, et al: Age-associated changes in electrophysiologic remodeling: a potential contributor to initiation of atrial fibrillation. Cardiovasc Res. 66:353–363. 2005. View Article : Google Scholar
6	Spach MS, Heidlage JF, Dolber PC and Barr RC: Mechanism of origin of conduction disturbances in aging human atrial bundles: experimental and model study. Heart Rhythm. 4:175–185. 2007. View Article : Google Scholar
7	Eisner DA, Diaz ME, Li Y, O’Neill SC and Trafford AW: Stability and instability of regulation of intracellular calcium. Exp Physiol. 90:3–12. 2005. View Article : Google Scholar : PubMed/NCBI
8	Katra RP and Laurita KR: Cellular mechanism of calcium-mediated triggered activity in the heart. Circ Res. 96:535–542. 2005. View Article : Google Scholar : PubMed/NCBI
9	van Wagoner DR, Pond AL, Lamorgese M, Rossie SS, McCarthy PM and Nerbonne JM: Atrial L-type Ca²⁺ currents and human atrial fibrillation. Circ Res. 85:428–436. 1999.
10	Croall DE and DeMartino GN: Calcium-activated neutral protease (calpain) system: structure, function, and regulation. Physiol Rev. 71:813–847. 1991.PubMed/NCBI
11	Brundel BJ, Ausma J, van Gelder IC, et al: Activation of proteolysis by calpains and structural changes in human paroxysmal and persistent atrial fibrillation. Cardiovasc Res. 54:380–389. 2002. View Article : Google Scholar : PubMed/NCBI
12	Daoud EG, Bogun F, Goyal R, et al: Effect of atrial fibrillation on atrial refractoriness in humans. Circulation. 94:1600–1606. 1996. View Article : Google Scholar : PubMed/NCBI
13	Ausma J, Dispersyn GD, Duimel H, et al: Changes in ultrastructural calcium distribution in goat atria during atrial fibrillation. J Mol Cell Cardiol. 32:355–364. 2000. View Article : Google Scholar : PubMed/NCBI
14	Allessie M, Ausma J and Schotten U: Electrical, contractile and structural remodeling during atrial fibrillation. Cardiovasc Res. 54:230–246. 2002. View Article : Google Scholar : PubMed/NCBI
15	Bers DM: Calcium cycling and signaling in cardiac myocytes. Annu Rev Physiol. 70:23–49. 2008. View Article : Google Scholar : PubMed/NCBI
16	Schiefer HB: Guide to the Care and Use of Experimental Animals, Volume 2. Can Vet J. 26:591985.
17	Yue L, Feng J, Gaspo R, Li GR, Wang Z and Nattel S: Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation. Circ Res. 81:512–525. 1997. View Article : Google Scholar : PubMed/NCBI
18	Bosch RF and Nattel S: Cellular electrophysiology of atrial fibrillation. Cardiovasc Res. 54:259–269. 2002. View Article : Google Scholar : PubMed/NCBI
19	Verheule S, Wilson E, Banthia S, et al: Direction-dependent conduction abnormalities in a canine model of atrial fibrillation due to chronic atrial dilatation. Am J Physiol Heart Circ Physiol. 287:H634–H644. 2004. View Article : Google Scholar : PubMed/NCBI
20	Wijffels MC, Kirchhof CJ, Dorland R and Allessie MA: Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation. 92:1954–1968. 1995. View Article : Google Scholar : PubMed/NCBI
21	Willems R, Holemans P, Ector H, Sipido KR, Van de Werf F and Heidbüchel H: Mind the model: effect of instrumentation on inducibility of atrial fibrillation in a sheep model. J Cardiovasc Electrophysiol. 13:62–67. 2002. View Article : Google Scholar : PubMed/NCBI
22	Nattel S, Khairy P and Schram G: Arrhythmogenic ionic remodelling: adaptive responses with maladaptive consequences. Trends Cardiovasc Med. 11:295–301. 2001. View Article : Google Scholar : PubMed/NCBI
23	Baba S, Dun W, Hirose M and Boyden PA: Sodium current function in adult and aged canine atrial cells. Am J Physiol Heart Circ Physiol. 291:H756–H761. 2006. View Article : Google Scholar : PubMed/NCBI
24	Tanaka K, Zlochiver S, Vikstrom KL, et al: Spatial distribution of fibrosis governs fibrillation wave dynamics in the posterior left atrium during heart failure. Circ Res. 101:839–847. 2007. View Article : Google Scholar : PubMed/NCBI
25	Wit AL and Boyden PA: Triggered activity and atrial fibrillation. Heart Rhythm. 4(Suppl 3): S17–S23. 2007. View Article : Google Scholar : PubMed/NCBI
26	Weiss JN, Qu Z, Chen PS, et al: The dynamics of cardiac fibrillation. Circulation. 112:1232–1240. 2005. View Article : Google Scholar : PubMed/NCBI
27	Everett TH IV and Olgin JE: Atrial fibrosis and the mechanisms of atrial fibrillation. Heart Rhythm. 4(Suppl 3): S24–S27. 2007. View Article : Google Scholar : PubMed/NCBI
28	Qu Z, Garfinkel A, Chen PS and Weiss JN: Mechanisms of discordant alternans and induction of reentry in simulated cardiac tissue. Circulation. 102:1664–1670. 2000. View Article : Google Scholar : PubMed/NCBI
29	Miragoli M, Gaudesius G and Rohr S: Electrotonic modulation of cardiac impulse conduction by myofibroblasts. Circ Res. 98:801–810. 2006. View Article : Google Scholar : PubMed/NCBI
30	Koura T, Hara M, Takeuchi S, et al: Anisotropic conduction properties in canine atria analyzed by high-resolution optical mapping: preferential direction of conduction block changes from longitudinal to transverse with increasing age. Circulation. 105:2092–2098. 2002. View Article : Google Scholar
31	Thijssen VL, Ausma J, Liu GS, Allessie MA, van Eys GJ and Borgers M: Structural changes of atrial myocardium during chronic atrial fibrillation. Cardiovasc Pathol. 9:17–28. 2000. View Article : Google Scholar : PubMed/NCBI
32	Mandapati R, Skanes A, Chen J, Berenfeld O and Jalife J: Stable microreentrant sources as a mechanism of atrial fibrillation in the isolated sheep heart. Circulation. 101:194–199. 2000.PubMed/NCBI
33	Ausma J, Wijffels M, Thoné F, Wouters L, Allessie M and Borgers M: Structural changes of atrial myocardium due to sustained atrial fibrillation in the goat. Circulation. 96:3157–3163. 1997. View Article : Google Scholar : PubMed/NCBI