NDLI: The mechanisms underlying I$_{Ca}$ heterogeneity across murine left ventricle

Content Provider	Springer Nature Link
Author	Xu, Lin Li, Xu Yong Liu, Yu Li, Hai Tao Chen, Jing Li, Xiao Yan Jiang, Xue Jun Wu, Gang Tang, Yan Hong Wang, Xi Huang, Cong Xin
Copyright Year	2011
Abstract	L-type calcium current (I$_{Ca}$) plays a critical role in excitation–contraction coupling (ECC). Unlike transient outward K$^{+}$ current (I$_{to}$), it is controversial whether I$_{Ca}$ transmural gradient exists in left ventricle. Although previous studies have shown some evidences for I$_{Ca}$ heterogeneity, the mechanism is still unknown. In this study, the authors recorded I$_{Ca}$ from epicardial (EPI) and endocardial (ENDO) myocytes isolated from murine left ventricle using patch-clamp technique. It was found that I$_{Ca}$ 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 I$_{Ca}$ 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 I$_{Ca}$ 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 I$_{Ca}$ heterogeneity in murine left ventricle.
Starting Page	239
Ending Page	246
Page Count	8
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	352
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Springer US
Publisher Date	2011-03-04
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	I$_{Ca}$ CaMKII p65 Cav1.2 Oncology Cardiology Medical Biochemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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