Max Delbrück Center for Molecular Medicine, Berlin Buch, Germany.
DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.
Biochem Soc Trans. 2020 Feb 28;48(1):39-49. doi: 10.1042/BST20190229.
Cardiac excitation-contraction coupling is initiated with the influx of Ca2+ ions across the plasma membrane through voltage-gated L-type calcium channels. This process is tightly regulated by modulation of the channel open probability and channel localization. Protein kinase A (PKA) is found in close association with the channel and is one of the main regulators of its function. Whether this kinase is modulating the channel open probability by phosphorylation of key residues or via alternative mechanisms is unclear. This review summarizes recent findings regarding the PKA-mediated channel modulation and will highlight recently discovered regulatory mechanisms that are independent of PKA activity and involve protein-protein interactions and channel localization.
心脏兴奋-收缩偶联是通过电压门控 L 型钙通道穿过质膜内流 Ca2+ 离子而引发的。该过程受通道开放概率和通道定位的调节。蛋白激酶 A(PKA)与通道密切相关,是其功能的主要调节剂之一。该激酶是通过磷酸化关键残基来调节通道的开放概率,还是通过其他机制尚不清楚。这篇综述总结了最近关于 PKA 介导的通道调节的发现,并强调了最近发现的与 PKA 活性无关的调节机制,涉及蛋白-蛋白相互作用和通道定位。