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L-VDCC autoregulation abnormality contributes to calcium overload in myocardial ischemia-reperfusion injury

YUE Zhi-Jie¹, SHI Zhan², Hu Bo², WANG Zhen-Guo², DU Yu-Lei^1,*

¹Department of Internal Medicine, Norman Bethune Military Medical College, Shijiazhuang 050081, China；²The 260th Hospital of People’s Liberation Army, Shijiazhuang 050047, China

Abstract

Calcium overload is a vital mechanism of myocardial ischemia-reperfusion injury, which is a hot therapeutic target in cardiovascular research. It has been well recognized that the dysfunction of calcium relevant proteins, including L-type voltage- dependent calcium channel (L-VDCC), sarco/endoplasmic reticulum ATPase 2a (SERCA2a)/phospholamban (PLB), RyR2, Na⁺/Ca²⁺ exchanger, Na⁺/H⁺ exchanger, etc. contributes to calcium overload in cardiomyocytes during ischemia-reperfusion injury, in which the diastolic calcium concentration is increased and the amplitude of calcium transients is decreased. There are two phases in calcium increase. The early phase is partially mediated by calcium channels, and the latter one is mainly mediated by Na⁺/Ca²⁺ exchanger. L-VDCC, a main subtype of calcium channels in myocardium, is involved in calcium overload, but the underlying molecular mechanism is not well elucidated yet. L-VDCC is regulated by intrinsic and extrinsic pathways. PKG and PKA as extrinsic regulators are not proper candidates to increase L-VDCC activity of cardiomyocyte in vitro, whereas the myocardial ischemia-reperfusion injury is highly possible to enhance L-VDCC activity by delaying calcium-dependent inactivation (CDI), advancing calcium-dependent facilitation (CDF), and weakening distal carboxy terminus (DCT) inhibition. Therefore, it is rational to propose that the L-VDCC autoregulation abnormality may play an important role in calcium overload during myocardial ischemia-reperfusion injury.

Key words: Heart; ischemia-reperfusion injury ; calcium overload ; L-type voltage-dependent calcium channel

Received: 2017-02-26　　Accepted: 2017-11-06

Corresponding author: 杜昱蕾　　E-mail: duyuyul@foxmail.com

DOI: 10.13294/j.aps.2017.0082

Citing This Article：

YUE Zhi-Jie, SHI Zhan, Hu Bo, WANG Zhen-Guo, DU Yu-Lei. L-VDCC autoregulation abnormality contributes to calcium overload in myocardial ischemia-reperfusion injury. Acta Physiol Sin 2017; 69 (6): 861-869 (in Chinese with English abstract).