The functional expression of transient receptor potential cation channel of the ankyrin-1 subtype (TRPA1) has recently been identified in adult mouse cardiac tissue where stimulation of this ion channel leads to increases in adult mouse ventricular cardiomyocyte (CM) contractile function via a Ca²⁺-Calmodulin-dependent kinase (CaMKII) pathway. However, the extent to which TRPA1 induces nitric oxide (NO) production in CMs, and whether this signaling cascade mediates physiological or pathophysiological events in cardiac tissue remains elusive. Freshly isolated CMs from wild-type (WT) or TRPA1 knockout (TRPA1^-/-) mouse hearts were treated with AITC (100 µM) and prepared for immunoblot, NO detection or ischemia protocols. Our findings demonstrate that TRPA1 stimulation with AITC results in phosphorylation of protein kinase B (Akt) and endothelial NOS (eNOS) concomitantly with NO production in a concentration- and time-dependent manner. Additionally, we found that TRPA1 induced increases in CM [Ca²⁺]_i and contractility occur independently of Akt and eNOS activation mechanisms. Further analysis revealed that the presence and activation of TRPA1 promotes CM survival and viability following ischemic insult via a mechanism partially dependent upon eNOS. Therefore, activation of the TRPA1/Akt/eNOS pathway attenuates ischemia-induced CM cell death.

最近在成年小鼠心脏组织中发现了锚蛋白1亚型（TRPA1）的瞬时受体电位阳离子通道的功能表达，其中该离子通道的刺激导致通过Ca ²增加成年小鼠心室心肌（CM）收缩功能⁺ -钙调蛋白依赖性激酶（CaMKII的）途径。但是，TRPA1诱导CM中一氧化氮（NO）产生的程度，以及该信号级联反应是否介导心脏组织中的生理或病理生理事件，仍然难以捉摸。从野生型（WT）或TRPA1敲除（TRPA1 ^-/-）小鼠心脏用AITC（100 µM）处理，并准备用于免疫印迹，NO检测或缺血方案。我们的发现表明，AITC刺激TRPA1会导致蛋白激酶B（Akt）和内皮NOS（eNOS）的磷酸化，并以浓度和时间依赖性方式产生NO。此外，我们发现TRPA1诱导CM [Ca ²⁺ ] _i的增加和收缩力独立于Akt和eNOS激活机制而发生。进一步的分析表明，通过局部依赖eNOS的机制，缺血性损伤后TRPA1的存在和激活可促进CM存活和生存能力。因此，TRPA1 / Akt / eNOS途径的激活减弱了缺血诱导的CM细胞死亡。