SM-102（1-辛基壬基 8-[（2-羥乙基）[6-氧代-6-（十一烷氧基）己基]氨基]-辛酸酯）是一種設計用以形成脂質奈米粒的陽離子胺基脂質，同時是莫德納COVID-19 mRNA疫苗中一種基本成分。然而，SM-102是否能影響不同類型的離子電流仍然未知。在本研究中，我們透過兩種內分泌細胞（例如大鼠腦下垂體腫瘤細胞GH3 cell和小鼠睪丸間質腫瘤細胞MA-10 cell）或微膠細胞BV2 cell來探討SM-102對細胞膜上離子電流的影響。我們將這些細胞放在高濃度K+、無Ca2+的細胞外液，並透過給予過極化電壓刺激產生K+電流，進而評估 SM-102對 erg介導的K+電流(IK(erg))的幅度和遲滯現象的影響。實驗結果發現，SM-102能有效阻斷IK(erg)，並且具有濃度依賴性，其半抑制濃度(IC50)為108 μM，接近於解離常數(KD)值（即 134 μM）。再者，透過等腰三角形斜坡的電壓改變所產生IK(erg) 的遲滯現象強度能被SM-102有效降低。另一方面，轉染試劑TurboFectinTM 8.0 (0.1 %, v/v)，也能有效地抑制過極化活化的 IK(erg)，同時增加電流的去活化的時間進程。此外，當GH3細胞用精胺(30 μM)透析後，IK(erg)的幅度逐漸減少；而近一步外加SM-102 (100 μM)或TurboFectin (0.1 %)能更加降低電流幅度。在MA-10 Leydig細胞中，IK(erg)也能因SM-102或TurboFectin的處理而抑制，其中，SM-102抑制MA-10細胞中IK(erg)的IC50為98 μM。另外，SM-102也能抑制BV2微膠細胞中的向內整流K+電流的幅度。總結以上，SM-102在內分泌細胞（例如，GH3 或MA-10細胞）中能濃度依賴性地抑制IK(erg)，若有相似的結果於體內研究發現，此作用可能有助於調整細胞的功能活性。

SM-102 is an amino cationic lipid that has been tailored for formation of lipid nanoparticles and it is one of essential ingredients contained in the ModernaTM COVID-19 vaccine. However, to what extent it may modify different types of membrane ionic currents remains largely unanswered. In the present study, we investigated the effects of SM-102 on ionic currents either in two types of endocrine cells (e.g., rat pituitary tumor [GH3] cells and mouse Leydig tumor [MA-10] cells) or in microglial (BV2) cells. Hyperpolarization-activated K+ currents in these cells bathed in high-K+, Ca2+-free extracellular solution were examined to assess effects of SM-102 on the amplitude and hysteresis of erg-mediated K+ current (IK(erg)). The presence of SM-102 showed inhibitory effect on IK(erg) in a concentration-dependent fashion with a half-maximal concentration (IC50) of 108 μM, a value which is closely near the KD value (i.e., 134 μM) required for its accentuation of deactivation time constant of the current. The hysteretic strength of IK(erg) in response to long-lasting isosceles-triangular ramp pulse was effectively decreased in the presence of SM-102. Cell exposure to TurboFectinTM 8.0 (0.1 %, v/v), a transfection reagent, was able to inhibit hyperpolarization-activated IK(erg) effectively with a raise in deactivation time course of the current. Additionally, in GH3 cells dialyzed with spermine (30 μM), IK(erg) amplitude progressively decreased; moreover, further bath application of SM-102 (100 μM) or TurboFectin (0.1 %) diminished current magnitude further. In MA-10 Leydig cells, the IK(erg) was also blocked by the presence of SM-102 or TurboFectin. The IC50 value for SM-102-induced inhibition of IK(erg) in MA-10 cells was estimated to be 98 μM. In BV2 microglial cells, the amplitude of inwardly rectifying K+ current was inhibited by SM-102. Collectively, the presence of SM-102 dose-dependently suppressed IK(erg) in endocrine cells (e.g., GH3 or MA-10 cells), and such action may be responsible for their functional activities, presuming that similar in vivo findings exist.

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