Residue Thr1604 in the CaV1.2 channel is a Ca2+/calmodulin dependent protein kinase II (CaMKII) phosphorylation site, and its phosphorylation status maintains the basic activity of the channel. However, the role of CaV1.2 phosphorylation at Thr1604 in myocardial hypertrophy is incompletely understood. Isoproterenol (ISO) was used to induce cardiomyocyte hypertrophy, and autocamtide-2-related inhibitory peptide (AIP) was added as a treatment. Rats in a myocardial hypertrophy development model were subcutaneously injected with ISO for two or three weeks. The heart and left ventricle weights, each of which were normalized to the body weight and cross-sectional area of the myocardial cells, were used to describe the degree of hypertrophy. Protein expression levels were detected by western blotting. CaMKII-induced CaV1.2 (Thr1604) phosphorylation (p-CaV1.2) was assayed by coimmunoprecipitation. The results showed that CaMKII, HDAC, MEF2 C, and atrial natriuretic peptide (ANP) expression was increased in the ISO group and downregulated by AIP treatment in vitro. There was no difference in the expression of these proteins between the ISO 2-week group and the ISO 3-week group in vivo. CaV1.2 channel expression did not change, but p-CaV1.2 expression was increased after ISO stimulation and decreased by AIP. In the rat model, p-CaV1.2 levels and CaMKII activity were much higher in the ISO 3-week group than in the ISO 2-week group. CaMKII-induced CaV1.2 channel phosphorylation at residue Thr1604 may be one of the key features of myocardial hypertrophy and disease development.Abbreviations: CaMKII: Ca2+/calmodulin dependent protein kinase II; p-CaMKII: autophosphorylated Ca2+/calmodulin dependent protein kinase II; CaM: calmodulin; AIP: autocamtide-2-related inhibitory peptide; ECC: excitation-contraction coupling; ISO: isoproterenol; BW: body weight; HW: heart weight; LVW: left ventricle weight; HDAC: histone deacetylase; p-HDAC: phosphorylated histone deacetylase; MEF2C: myocyte-specific enhancer factor 2C; ANP: atrial natriuretic peptide; PKC: protein kinase C.

中文翻译：

---

CaV1.2通道中的CaMKII磷酸化位点Thr1604与大鼠病理性心肌肥大有关。

CaV1.2通道中的残基Thr1604是一个Ca2 + /钙调蛋白依赖性蛋白激酶II（CaMKII）磷酸化位点，其磷酸化状态维持该通道的基本活性。但是，尚不清楚Thr1604处CaV1.2磷酸化在心肌肥大中的作用。使用异丙肾上腺素（ISO）诱导心肌肥大，并加入与autocamtide-2相关的抑制肽（AIP）作为治疗药物。在心肌肥大发展模型中的大鼠皮下注射ISO两到三周。心脏和左心室的重量（均已根据体重和心肌细胞的横截面积标准化）用于描述肥大程度。通过蛋白质印迹检测蛋白质表达水平。CaMKII诱导的CaV1。通过共免疫沉淀法测定2（Thr1604）磷酸化（p-CaV1.2）。结果表明，ISO组中CaMKII，HDAC，MEF2 C和心钠素（ANP）的表达增加，而体外AIP处理则下调了其表达。在体内ISO 2周组和ISO 3周组之间，这些蛋白质的表达没有差异。CaV1.2通道表达没有改变，但p-CaV1.2表达在ISO刺激后增加，而AIP降低。在大鼠模型中，ISO 3周组的p-CaV1.2水平和CaMKII活性远高于ISO 2周组。CaMKII诱导的残基Thr1604处CaV1.2通道的磷酸化可能是心肌肥大和疾病发展的关键特征之一。p-CaMKII：自磷酸化的Ca2 + /钙调蛋白依赖性蛋白激酶II; CaM：钙调蛋白；AIP：autocamtide-2相关抑制肽；ECC：激励－收缩耦合；ISO：异丙肾上腺素；BW：体重；硬件：心脏重量；LVW：左心室重量；HDAC：组蛋白脱乙酰基酶；p-HDAC：磷酸化的组蛋白脱乙酰基酶；MEF2C：肌细胞特异性增强因子2C；ANP：心钠素；PKC：蛋白激酶C。