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(TM) 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(3)) 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(2+)-free extracellular solution were examined to assess the effects of SM-102 on the amplitude and hysteresis of the erg-mediated K(+) current (I(K(erg))). The SM-102 addition was effective at blocking I(K(erg)) in a concentration-dependent fashion with a half-maximal concentration (IC(50)) of 108 μM, a value which is similar to the K(D) value (i.e., 134 μM) required for its accentuation of deactivation time constant of the current. The hysteretic strength of I(K(erg)) in response to the long-lasting isosceles-triangular ramp pulse was effectively decreased in the presence of SM-102. Cell exposure to TurboFectin(TM) 8.0 (0.1%, v/v), a transfection reagent, was able to inhibit hyperpolarization-activated I(K(erg)) effectively with an increase in the deactivation time course of the current. Additionally, in GH(3) cells dialyzed with spermine (30 μM), the I(K(erg)) 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(K(erg)) was also blocked by the presence of SM-102 or TurboFectin. The IC(50) value for SM-102-induced inhibition of I(K(erg)) 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(K(erg)) in endocrine cells (e.g., GH(3) or MA-10 cells), and such action may contribute to their functional activities, assuming that similar in vivo findings exist.
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