首页> 外文期刊>Cellular Physiology and Biochemistry >Neuromedin S Increases L-type Ca2+ Channel Currents Through Giα-protein and Phospholipase C-dependent Novel Protein Kinase C Delta Pathway in Adult Rat Ventricular Myocytes
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Neuromedin S Increases L-type Ca2+ Channel Currents Through Giα-protein and Phospholipase C-dependent Novel Protein Kinase C Delta Pathway in Adult Rat Ventricular Myocytes

机译:Neuromedin S通过成年大鼠心室肌细胞中的Giα蛋白和磷脂酶C依赖的新型蛋白激酶C Delta途径增加L型Ca2 +通道电流

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Neuromedin S (NMS), a peptide structurally related to NMU, has been identified in the mammalian heart tissues. However to date, any role of NMS in cardiomyocytes and the relevant mechanisms still remain unknown. In this study, we identified a novel functional role of NMS in modulating L-type Casup2+/sup channels in adult rat ventricular myocytes, in which NMU type 2 receptors (NMUR2), but not NMUR1, are endogenously expressed. We found that NMS at 0.1 µM reversibly increased IsubBa /subby ~29.7%. Intracellular infusion of GDP-β-S or a selective antibody raised against the Gsubi/sub-protein blocked the stimulatory effects of NMS. The classical and novel protein kinase C (nPKC) antagonist calphostin C or chelerythrine chloride, as well as the phospholipase C (PLC) inhibitor U73122, abolished NMS responses, whereas a classical PKC antagonist Gö6976 or a PKA antagonist PKI 5-24 had no such effects. Pretreatment of cells with PKC-δ specific inhibitor rottlerin or intracellular application of a PKC-δ-derived inhibitory peptide, δV1-1, abolished NMS responses, while an inactive control peptide had no effects. In summary, NMS acting through NMUR2 increases IsubBa /subvia a Gsubi/subα-protein-dependent PKC-δ pathway in rat ventricular myocytes.
机译:Neuromedin S(NMS)是一种与NMU结构相关的肽,已在哺乳动物心脏组织中得到鉴定。然而,迄今为止,NMS在心肌细胞中的任何作用及其相关机制仍然未知。在这项研究中,我们发现了NMS在调节成年大鼠心室肌细胞L型Ca 2 + 通道中的新功能,其中NMU 2型受体(NMUR2)而非NMUR1是内源性的表达。我们发现,0.1 µM的NMS可逆地将I Ba 提高了〜29.7%。细胞内输注GDP-β-S或抗G i 蛋白的选择性抗体可阻断NMS的刺激作用。经典和新型蛋白激酶C(nPKC)拮抗剂钙磷蛋白C或白屈菜红碱氯化物,以及磷脂酶C(PLC)抑制剂U73122消除了NMS反应,而经典PKC拮抗剂Gö6976或PKA拮抗剂PKI 5-24没有这种作用效果。用PKC-δ特异性抑制剂rottlerin预处理细胞或在细胞内应用PKC-δ衍生的抑制肽δV1-1可以消除NMS反应,而无活性的对照肽则没有作用。总之,通过NMUR2作用的NMS通过G i α蛋白依赖性PKC-δ途径增加大鼠心室肌细胞的I Ba

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