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The mechanisms underlying ICa heterogeneity across murine left ventricle

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Abstract

L-type calcium current (ICa) plays a critical role in excitation–contraction coupling (ECC). Unlike transient outward K+ current (Ito), it is controversial whether ICa transmural gradient exists in left ventricle. Although previous studies have shown some evidences for ICa heterogeneity, the mechanism is still unknown. In this study, the authors recorded ICa from epicardial (EPI) and endocardial (ENDO) myocytes isolated from murine left ventricle using patch-clamp technique. It was found that ICa density was obviously larger in EPI than in ENDO (7.3 ± 0.3 pA/pF vs. 6.2 ± 0.2 pA/pF, at test potential of +10 mV, P < 0.05). The characteristics of ICa showed no difference between these two regions except for the fast inactivation time constants (9.9 ± 0.9 ms in EPI vs. 13.5 ± 0.9 ms in ENDO, at test potential of +10 mV, P < 0.05). In addition, it was explored the molecular mechanism underlying ICa transmural gradient by Western blot. The authors demonstrated that a higher activity of CaMKII in ENDO cells induced more nuclear translocation of p65, a component of nuclear factor-kappa B (NF-kB). Consequently, p65 in ENDO inhibited more transcription of Cav1.2, the main encoding gene for L-type calcium channels (LTCCs). These results reveal a difference in CaMKII/p65 signal pathway between EPI and ENDO that underlies this mechanism of ICa heterogeneity in murine left ventricle.

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Acknowledgment

This study was supported by Eleventh Five-year Priority Projects of Hubei Science and Technology Department, China (no. 2006A301A04) and the National 211 Priority Projects of Wuhan University.

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Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China

    Lin Xu, Xu-Yong Li, Yu Liu, Hai-Tao Li, Jing Chen, Xiao-Yan Li, Xue-Jun Jiang, Gang Wu, Yan-Hong Tang, Xi Wang & Cong-Xin Huang

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  1. Lin Xu
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  2. Xu-Yong Li
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  3. Yu Liu
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Correspondence to Cong-Xin Huang.

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Xu, L., Li, XY., Liu, Y. et al. The mechanisms underlying ICa heterogeneity across murine left ventricle. Mol Cell Biochem 352, 239–246 (2011). https://doi.org/10.1007/s11010-011-0759-8

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