Kumari Neema, Gaur Himanshu, Bhargava Anamika
Ion Channel Biology Lab, Department of Biotechnology, Indian Institute of Technology Hyderabad, Telangana 502285, India.
Ion Channel Biology Lab, Department of Biotechnology, Indian Institute of Technology Hyderabad, Telangana 502285, India.
Life Sci. 2018 Feb 1;194:139-149. doi: 10.1016/j.lfs.2017.12.033. Epub 2017 Dec 27.
Voltage-gated calcium channels (VGCCs) are the predominant source of calcium influx in the heart leading to calcium-induced calcium release and ultimately excitation-contraction coupling. In the heart, VGCCs are modulated by the β-adrenergic signaling. Signaling through β-adrenergic receptors (βARs) and modulation of VGCCs by β-adrenergic signaling in the heart are critical signaling and changes to these have been significantly implicated in heart failure. However, data related to calcium channel dysfunction in heart failure is divergent and contradictory ranging from reduced function to no change in the calcium current. Many recent studies have highlighted the importance of functional and spatial microdomains in the heart and that may be the key to answer several puzzling questions. In this review, we have briefly discussed the types of VGCCs found in heart tissues, their structure, and significance in the normal and pathological condition of the heart. More importantly, we have reviewed the modulation of VGCCs by βARs in normal and pathological conditions incorporating functional and structural aspects. There are different types of βARs, each having their own significance in the functioning of the heart. Finally, we emphasize the importance of location of proteins as it relates to their function and modulation by co-signaling molecules. Its implication on the studies of heart failure is speculated.
电压门控性钙通道（VGCCs）是心脏中钙内流的主要来源，可导致钙诱导的钙释放，并最终引发兴奋-收缩偶联。在心脏中，VGCCs受β-肾上腺素能信号通路调节。通过β-肾上腺素能受体（βARs）的信号传导以及心脏中β-肾上腺素能信号通路对VGCCs的调节是关键的信号传导，而这些信号传导的改变与心力衰竭密切相关。然而，与心力衰竭中钙通道功能障碍相关的数据存在分歧且相互矛盾，从钙电流功能降低到无变化不等。最近的许多研究都强调了心脏中功能和空间微区的重要性，这可能是解答几个令人困惑问题的关键。在这篇综述中，我们简要讨论了心脏组织中发现的VGCCs的类型、它们的结构以及在心脏正常和病理状态下的意义。更重要的是，我们结合功能和结构方面，综述了正常和病理状态下βARs对VGCCs的调节。存在不同类型的βARs，每种在心脏功能中都有其自身的意义。最后，我们强调蛋白质位置与其功能以及共信号分子调节之间关系的重要性。推测了其对心力衰竭研究的意义。
