| Abstract [eng] |
Voltage-gated ion channels regulate essential cellular processes in both excitable and non-excitable cells. Number of factors can modify their activity. Moreover, mutations may alter the biophysical properties of ion channels and result in pathological states. This dissertation is based on two studies investigating ion channel function. Study I examined the effects of TGF-β3 and IL-1β on L-type voltage-gated calcium channels (L-VGCCs) activity and Ca²⁺ homeostasis in osteoarthritic chondrocytes and human bone marrow-derived mesenchymal stem cells during chondrogenesis. The results demonstrated cell type-specific regulation of L-VGCC function and intracellular Ca²⁺ homeostasis by TGF-β3, whereas IL-1β had no significant effect under the experimental conditions. Study II investigated the functional consequences of the KCNQ1 potassium channel gene variant c.1111G>C [p.(Ala371Pro)] associated with Long QT Syndrome (LQTS). Functional characterization revealed that the p.Ala371Pro variant markedly reduced IKs current by decreasing channel conductance without affecting voltage-dependent activation, supporting its pathogenic role in LQTS. Although addressing different biological questions, both studies are united by the application of biophysical approach - whole-cell patch-clamp electrophysiology, to investigate ion channel function. |
