| Abstract [eng] |
Genetic mutations affecting ion channel function can lead to various cardiac rhythm disorders. One of these disorders is long QT syndrome (LQTS), which is characterized by delayed repolariza-tion of the cardiac action potential. The slow delayed rectifier potassium current (IKs), important for maintaining cardiac electrical stability, is generated by the KCNQ1/KCNE1 channel complex. Muta-tions in the KCNQ1 gene may alter channel conductance, voltage-dependent activation, and kinetic properties, thereby contributing to the development of the LQT1 phenotype. One of the identified pathogenic variants is KCNQ1 p.(Ala371Pro). Since electrophysiological results obtained in previous studies did not fully correspond to the KCNQ1/KCNE1 channel properties described in the literature, the potential influence of the human embryonic kidney (HEK) cell source on the recorded channel parameters was additionally evaluated in this study. The aim of this study was to determine the effect of the KCNQ1 p.(Ala371Pro) variant on the activation properties of KCNQ1/KCNE1 channels. Whole-cell voltage clamp recordings were used to measure IKs currents during depolarization step protocols. Current density, voltage-dependent con-ductance, half-activation potential, and activation and deactivation kinetics were evaluated. Addition-ally, activation properties of wild-type KCNQ1/KCNE1 channels were compared between two dif-ferent HEK cell sources to assess the potential influence of cell source on the recorded channel prop-erties. The results showed that channels expressed in the second HEK cell source exhibited higher cur-rent density, greater maximal conductance, and kinetic properties more characteristic of the KCNQ1/KCNE1 complex compared to the first cell source. The KCNQ1 p.(Ala371Pro) variant significantly reduced current density and maximal conductance, shifted the half-activation potential toward more depolarized membrane potentials, and altered channel activation kinetics. Currents gen-erated by the variant lacked the exponential activation behavior characteristic of wild-type channels. These findings indicate that the KCNQ1 p.(Ala371Pro) variant impairs KCNQ1/KCNE1 channel function and may contribute to impaired cardiac repolarization and the development of the LQT1 phenotype. |
