Structural and functional remodeling of the atrioventricular node with aging in rats: The role of hyperpolarization-activated cyclic nucleotide–gated and ryanodine 2 channels
| Autor: | Saeed, Yawer, Temple, Ian, Borbas, Zoltan, Atkinson, Andrew, Yanni Gerges, Joseph, Maczewski, Michał, Mackiewicz, U., Aly, M, Logantha, Sunil, Garratt, Clifford, Dobrzynski, Halina |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
Aging Patch-Clamp Techniques If Ryanodine ion channel expression Ryanodine Receptor Calcium Release Channel Ion channel expression Immunohistochemistry Article Rats ageing Models Animal cardiovascular system Atrioventricular Node Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Animals ryanodine AV node Rats Wistar f current |
| Zdroj: | Heart Rhythm Saeed, Y, Temple, I P, Borbas, Z, Atkinson, A, Yanni Gerges, J, Maczewski, M, Mackiewicz, U, Aly, M, Logantha, S, Garratt, C & Dobrzynski, H 2018, ' Structural and functional remodeling of the atrioventricular node with aging in rats: The role of hyperpolarization-activated cyclic nucleotide-gated and ryanodine 2 channels ', Heart Rhythm . https://doi.org/10.1016/j.hrthm.2017.12.027 Saeed, Y, Temple, I, Borbas, Z, Atkinson, A, Yanni Gerges, J, Maczewski, M, Mackiewicz, U, Aly, M, Logantha, S, Garratt, C & Dobrzynski, H 2017, ' Structural and functional remodeling of the atrioventricular node with aging in rats: The role of hyperpolarization-activated cyclic nucleotide-gated and ryanodine 2 channels ' Heart Rhythm . DOI: 10.1016/j.hrthm.2017.12.027 |
| ISSN: | 1556-3871 1547-5271 |
| DOI: | 10.1016/j.hrthm.2017.12.027 |
| Popis: | Background Aging is associated with an increased incidence of atrioventricular nodal (AVN) dysfunction. Objective The aim of this study was to investigate the structural and functional remodeling in the atrioventricular junction (AVJ) with aging. Methods Electrophysiology, histology, and immunohistochemistry experiments on male Wistar Hannover rats aged 3 months (n = 24) and 2 years (n = 15) were performed. Atrio-His (AH) interval, Wenkebach cycle length (WBCL), and AVN effective refractory period (AVNERP) were measured. Cesium (2 mM) was used to block hyperpolarization-activated cyclic nucleotide–gated (HCN) channels, while ryanodine (2 μM) was used to block ryanodine 2 (RyR2) channels. Protein expression from different regions of the AVJ was studied using immunofluorescence. The expression of connexins (connexin 43 and connexin 40), ion channels (Hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), voltage sensitive sodium channel (Nav1.5), and L-Type calcium channel (Cav1.3)), and calcium handling proteins (RyR2 and sarco/endoplasmic reticulum calcium ATPaset type 2a (SERCA2a)) were measured. Morphological characteristics were studied with histology. Results Without drugs to block HCN and RyR2 channels, there was prolongation of the AH interval, WBCL, and AVNERP (P < .05) with aging. In young rats only, cesium prolonged the AH interval, WBCL, and AVNERP (P < .01). Ryanodine prolonged the AH interval and WBCL (P < .01) in both young and old rats. Immunofluorescence revealed that with aging, connexin 43, HCN4, Nav1.5, and RyR2 downregulate in the regions of the AVJ and connexin 40, SERCA2a, and Cav1.3 upregulate (P < .05). Aging results in cellular hypertrophy, loosely packed cells, a decrease in the number of nuclei, and an increase in collagen content. Conclusion Heterogeneous ion channel expression changes were observed in the AVJ with aging. For the first time, we have shown that HCN and RyR2 play an important role in AVN dysfunction with aging. |
| Databáze: | OpenAIRE |
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