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Emerging Concepts in Ion Channel Biophysics
Poster Abstracts
93
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.