Muscle Dysfunction Caused by a K ATP Channel Mutation in Neonatal Diabetes Is Neuronal in Origin

• DOI: 10.1126/science.1186146
• Publication Date: 2010-07-02T02:41:04Z
• Authors: Rebecca H. Clark; James S. McTaggart; Richard Webster; Roope Mannikko; Michaela Iberl; Xiu Li Sim; Patrik Rorsman; Maike Glitsch; David Beeson; Frances M. Ashcroft
• Keywords: Adenosine triphosphate; Muscle weakness; Kir6.2

Gain-of-function mutations in Kir6.2 (KCNJ11), the pore-forming subunit of adenosine triphosphate (ATP)-sensitive potassium (KATP) channel, cause neonatal diabetes. Many patients also suffer from hypotonia (weak and flaccid muscles) balance problems. The diabetes arises suppressed insulin secretion by overactive KATP channels pancreatic beta-cells, but source motor phenotype is unknown. By using mice carrying a human mutation (Val59-->Met59) targeted to either muscle or nerve, we show that analogous impairments originate central nervous system rather than peripheral nerves. We identify locomotor hyperactivity as feature channel overactivity. These findings suggest drugs against neuronal, muscle, are needed treat deficits such require high blood-brain barrier permeability.