Modulation of Ca2+ Activity in Cardiomyocytes through Caveolae-Gαq Interactions
Modulation of Ca2+ Activity in Cardiomyocytes through Caveolae-Gαq Interactions
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DOI：
10.1016/j.bpj.2011.02.013
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发表时间：
2011-04-06
影响因子：
3.4
通讯作者：
Scarlata, Suzanne
中科院分区：
文献类型：
--
作者：
Guo, Yuanjian;Golebiewska, Urszula;Scarlata, Suzanne
心肌细胞具有复杂的Ca 2+行为，这种行为的变化可能是某些疾病状态的基础。细胞内Ca 2+活性可通过位于质膜上的磷脂酶C β-G α（q）途径调节。心肌细胞的质膜富含由小窝蛋白组织的小窝结构域。小窝可能通过捕获和定位特定蛋白质间接影响细胞信号。最近，我们发现小窝蛋白可能与激活的G α（q）特异性相互作用，从而影响Ca 2+信号。在这里，使用荧光成像和相关技术，我们表明，G α（q）-G β γ亚基定位于小窝在成年犬心室心肌细胞。卡巴胆碱刺激从小窝释放G β γ亚基，同时通过小窝蛋白-3（Cav 3）稳定活化的G α（q）。这些细胞显示振荡的Ca 2+波，这在不含Cav 3的新生细胞中是看不到的。显微注射一种肽，破坏Cav 3-G α（q）的协会，但不是一个控制肽，消除波。此外，这些波在雷诺定处理下没有变化，但在磷脂酶C抑制剂处理下没有观察到，这意味着Cav 3-G α（q）负责这种Ca 2+活性。综上所述，这些研究表明，小窝在调节心肌细胞中的基础Ca 2+活性中发挥直接和积极的作用。
Cardiomyocytes have a complex Ca2+ behavior and changes in this behavior may underlie certain disease states. Intracellular Ca2+ activity can be regulated by the phospholipase C beta-G alpha(q) pathway localized on the plasma membrane. The plasma membranes of cardiomycoytes are rich in caveolae domains organized by caveolin proteins. Caveolae may indirectly affect cell signals by entrapping and localizing specific proteins. Recently, we found that caveolin may specifically interact with activated G alpha(q), which could affect Ca2+ signals. Here, using fluorescence imaging and correlation techniques we show that G alpha(q)-G beta gamma subunits localize to caveolae in adult ventricular canine cardiomyoctyes. Carbachol stimulation releases G beta gamma subunits from caveolae with a concurrent stabilization of activated G alpha(q) by caveolin-3 (Cav3). These cells show oscillating Ca2+ waves that are not seen in neonatal cells that do not contain Cav3. Microinjection of a peptide that disrupts Cav3-G alpha(q) association, but not a control peptide, extinguishes the waves. Furthermore, these waves are unchanged with rynaodine treatment, but not seen with treatment of a phospholipase C inhibitor, implying that Cav3-G alpha(q) is responsible for this Ca2+ activity. Taken together, these studies show that caveolae play a direct and active role in regulating basal Ca2+ activity in cardiomyocytes.