Department of Pediatrics, Division of Molecular Cardiovascular Biology, Howard Hughes Medical Institute, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH 45229-3039, USA.
Circ Res. 2011 Jan 21;108(2):265-72. doi: 10.1161/CIRCRESAHA.110.225888.
Transient receptor potential (TRP) channels of multiple subclasses are expressed in the heart, although their functions are only now beginning to emerge, especially for the TRPC subclass that appears to regulate the cardiac hypertrophic response. Although TRP channels permeate many different cations, they are most often ascribed a specific biological function because of Ca(2+) influx, either for microdomain signaling or to reload internal Ca(2+) stores in the endoplasmic reticulum through a store-operated mechanism. However, adult cardiac myocytes arguably do not require store-operated Ca(2+) entry to regulate sarcoplasmic reticulum Ca(2+) levels and excitation-contraction coupling; hence, TRP channels expressed in the heart most likely coordinate signaling within local domains or through direct interaction with Ca(2+)-dependent regulatory proteins. Here, we review the emerging evidence that TRP channels, especially TRPCs, are critical regulators of microdomain signaling in the heart to control pathological hypertrophy in coordination with signaling through effectors such as calcineurin and NFAT (nuclear factor of activated T cells).
瞬时受体电位 (TRP) 通道有多个亚类表达在心脏中，尽管它们的功能才刚刚开始显现，特别是对于似乎调节心脏肥厚反应的 TRPC 亚类。尽管 TRP 通道可以渗透许多不同的阳离子，但由于 Ca(2+) 内流，它们通常被赋予特定的生物学功能，无论是用于微域信号转导还是通过储存操作机制来重新填充内质网中的内部 Ca(2+) 储存。然而，成年心肌细胞可能不需要储存操作 Ca(2+) 内流来调节肌浆网 Ca(2+) 水平和兴奋-收缩偶联；因此，在心脏中表达的 TRP 通道很可能通过与 Ca(2+) 依赖性调节蛋白的直接相互作用或通过局部域内的信号转导来协调信号转导。在这里，我们回顾了新兴的证据，表明 TRP 通道，特别是 TRPC，是心脏微域信号转导的关键调节剂，可与钙调神经磷酸酶和 NFAT（激活 T 细胞的核因子）等效应器协调控制病理性肥厚。
