Voltage-Dependent Gating in a “Voltage Sensor-Less” Ion Channel

An unusual mechanism of ion channel regulation generates voltage-dependent gating in the absence of a canonical voltage-sensing domain

Nano-colloid printing of functionalised PLA-b-PEO copolymers: Tailoring the surface pattern of adhesive motif and its effect on cell attachment

n this study, we investigate the preparation of surface pattern of functional groups on poly(lactide) (PLA) surfaces through the controlled deposition of core-shell self-assemblies based on functionalized PLA-b-PEO amphiphilic block copolymers from selective solvents. Through grafting RGDS peptide onto the functionalized copolymer surface, the presented approach enables to prepare PLA surfaces with random and clustered spatial distribution of adhesive motifs. The proposed topography of the adhesion motif was proved by atomic force microscopy techniques using biotin-tagged RGDS peptide grafted on the surface and streptavidin-modified gold nanospheres which bind the tagged RGDS peptides as a contrast agent. The cell culture study under static and dynamic conditions with MG63 osteosarcoma cell line showed that the clustered distribution of RGDS peptides provided more efficient initial cell attachment and spreading, and resistance to cell detachment under dynamic culture compared to randomly distributed RGDS motif when with the same average RGDS peptide concentration

Neonatal diabetes caused by homozygous KCNJ11 mutation demonstrates that tiny changes in ATP sensititvity markedly affect diabetes risk

Aims/hypothesis The pancreatic ATP-sensitive potassium (KATP) channel plays a pivotal role in linking beta cell metabolism to insulin secretion. Mutations in KATP channel genes can result in hypo- or hypersecretion of insulin, as in neonatal diabetes mellitus and congenital hyperinsulinism, respectively. To date, all patients affected by neonatal diabetes due to a mutation in the pore-forming subunit of the channel (Kir6.2, KCNJ11) are heterozygous for the mutation. Here, we report the first clinical case of neonatal diabetes caused by a homozygous KCNJ11 mutation. Methods A male patient was diagnosed with diabetes shortly after birth. At 5 months of age, genetic testing revealed he carried a homozygous KCNJ11 mutation, G324R, (Kir6.2-G324R) and he was successfully transferred to sulfonylurea therapy (0.2 mg kg−1 day−1). Neither heterozygous parent was affected. Functional properties of wild-type, heterozygous and homozygous mutant KATP channels were examined after heterologous expression in Xenopus oocytes. Results Functional studies indicated that the Kir6.2-G324R mutation reduces the channel ATP sensitivity but that the difference in ATP inhibition between homozygous and heterozygous channels is remarkably small. Nevertheless, the homozygous patient developed neonatal diabetes, whereas the heterozygous parents were, and remain, unaffected. Kir6.2-G324R channels were fully shut by the sulfonylurea tolbutamide, which explains why the patient’s diabetes was well controlled by sulfonylurea therapy. Conclusions/interpretation The data demonstrate that tiny changes in KATP channel activity can alter beta cell electrical activity and insulin secretion sufficiently to cause diabetes. They also aid our understanding of how the Kir6.2-E23K variant predisposes to type 2 diabetes. </p

Neonatal diabetes caused by a homozygous KCNJ11 mutation demonstrates that tiny changes in ATP sensitivity markedly affect diabetes risk.

The pancreatic ATP-sensitive potassium (KATP) channel plays a pivotal role in linking beta cell metabolism to insulin secretion. Mutations in KATP channel genes can result in hypo- or hypersecretion of insulin, as in neonatal diabetes mellitus and congenital hyperinsulinism, respectively. To date, all patients affected by neonatal diabetes due to a mutation in the pore-forming subunit of the channel (Kir6.2, KCNJ11) are heterozygous for the mutation. Here, we report the first clinical case of neonatal diabetes caused by a homozygous KCNJ11 mutation.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site