Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Poster Abstracts

9-POS Board 9 Insights into the Role of the Kir2.1 K + Channel during Osteoblastogenesis Julia Matonti 1 , Jonathan Pini 1 , Serena Giuliano 1 , Dina Simkin 2 , Matthieu Rouleau 1 , Saïd Bendahhou 1 . 1 UMR7370 CNRS - Université Côte d'Azur, Nice, France, 2 Northwestern University, Chicago, IL, USA. The inwardly rectifying K + channel Kir2.1 is widely expressed in excitable and non-excitable tissues, and is encoded by the KCNJ2 gene. It plays a key role in maintaining the resting membrane potential in excitable tissues, and ensures the late repolarization phase in the cardiac action potential. Mutations on the KCNJ2 gene have been associated with Andersen’s syndrome, short QT syndrome (SQT3), and atrial fibrillation. Andersen’s syndrome (AS) is a rare and complex disorder presenting with skeletal muscle, cardiac muscle, and bone defects. AS- associated heterozygous de novo mutations lead to a loss of Kir2.1-associated inwardly rectifying current due to the dominant-negative nature of the disorder. While the function of the Kir2.1 channel can be anticipated in excitable cells, its role in bone development remains to be elucidated. We have generated human induced pluripotent stem (iPS) cells from healthy and AS patient muscular biopsies and have shown that this can be a good model for AS disorder. These cells were used to investigate the impact of Kir2.1 loss of function during osteoblast differentiation. We show that loss of Kir2.1 channel function down regulates master gene expression during the osteoblast differentiation, leading to defective osteoblasts. This down regulation is due to a disruption of the Bone Morphogenetic Proteins (BMP) signaling pathway. Our work reveals how the electrogenic activity of Kir2.1 K + channels at the cell surface can control intracellular signaling.

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