Effective Perturbations on the Amplitude and Hysteresis of Erg-Mediated Potassium Current Caused by 1-Octylnonyl 8-[(2-hydroxyethyl)[6-oxo-6(undecyloxy)hexyl]amino]-octanoate (SM-102), a Cationic Lipid.

SM-102 (1-octylnonyl 8-[(2-hydroxyethyl)[6-oxo-6-(undecyloxy)hexyl]amino]-octanoate) is an amino cationic lipid that has been tailored for the formation of lipid nanoparticles and it is one of the essential ingredients present in the Moderna COVID-19 vaccine. However, to what extent it may modify varying types of plasmalemmal ionic currents remains largely uncertain. In this study, we investigate the effects of SM-102 on ionic currents either in two types of endocrine cells (e.g., rat pituitary tumor (GH) cells and mouse Leydig tumor (MA-10) cells) or in microglial (BV2) cells. Hyperpolarization-activated K currents in these cells bathed in high-K, Ca-free extracellular solution were examined to assess the effects of SM-102 on the amplitude and hysteresis of the erg-mediated K current (I). The SM-102 addition was effective at blocking I in a concentration-dependent fashion with a half-maximal concentration (IC) of 108 μM, a value which is similar to the K value (i.e., 134 μM) required for its accentuation of deactivation time constant of the current. The hysteretic strength of I in response to the long-lasting isosceles-triangular ramp pulse was effectively decreased in the presence of SM-102. Cell exposure to TurboFectin 8.0 (0.1%, /), a transfection reagent, was able to inhibit hyperpolarization-activated I effectively with an increase in the deactivation time course of the current. Additionally, in GH cells dialyzed with spermine (30 μM), the I amplitude progressively decreased; moreover, a further bath application of SM-102 (100 μM) or TurboFectin (0.1%) diminished the current magnitude further. In MA-10 Leydig cells, the I was also blocked by the presence of SM-102 or TurboFectin. The IC value for SM-102-induced inhibition of I in MA-10 cells was 98 μM. In BV2 microglial cells, the amplitude of the inwardly rectifying K current was inhibited by SM-102. Taken together, the presence of SM-102 concentration-dependently inhibited I in endocrine cells (e.g., GH or MA-10 cells), and such action may contribute to their functional activities, assuming that similar in vivo findings exist.