[No authors listed]
Early repolarization syndrome (ERS) is associated with genetic mutations, but the role of the glycerolâ3âphosphate dehydrogenase 1âlike (GPD1âL) mutation remains unclear. The aim of the present study was to investigate the role and potential underlying mechanism of GPD1âL mutation P112L in the pathogenesis of ERS. Wholeâgenome sequencing was performed on samples from a family with ERS, and the gene sequencing results were analyzed using bioinformatics. 293Â cells were transfected with wildâtype (WT) or mutantâtype (MT) GPD1âL and SCN5A plasmids. Successful transfection of GPD1âL in 293Â cells was verified by western blotting. Wholeâcell patchâclamp recording, confocal microscopic observation and western blotting were used to uncover the potential mechanism of GPD1âL P112L in ERS. The results of western blotting indicated that the expression of the GPD1âL protein was lower in the MT group compared with that in the WT group, but the mock group did not express the GPD1âL protein. The wholeâcell patchâclamp recording results indicated that the activation current density of INa (at â30Â mV) was ~60% lower in the MT group compared with the WT group (P<0.01). The mutation caused the inactivation voltage to move in a negative direction by ~3Â mV compared with that of the WT group. However, there were no significant betweenâgroup differences in the steady activation, steady inactivation, and steady recovery of INa. Confocal microscopy demonstrated that MT GPD1âL was less expressed near the cell membrane and more expressed in the cytoplasm compared with WT GPD1âL. Both WT and MT GPD1âL were highly expressed in the cytoplasm and in small amounts in the nucleus. In conclusion, the GPD1âL P112L mutation decreased INa activation and GPD1âL cell expression, including in the region near the cell membrane. These results suggest that GPD1âL P112L may be a pathogenic genetic mutation associated with ERS.
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