Anti-KCNK2 (N-terminal) polyclonal antibody

Development of the cerebral cortex depends partly on neural activity, but the identity of the ion channels that might contribute to the activity-dependent cortical development is unknown. KCNK channels are critical determinants of neuronal excitability in the mature cerebral cortex, and a member of the KCNK family, KCNK9, is responsible for a maternally transmitted mental retardation syndrome. Here, we have investigated the roles of KCNK family potassium channels in cortical development. Knockdown of KCNK2, 9, or 10 by RNAi using in utero electroporation impaired the migration of late-born cortical excitatory neurons destined to become Layer II/III neurons. The migration defect caused by KCNK9 knockdown was rescued by coexpression of RNAi-resistant functional KCNK9 mutant. Furthermore, expression of dominant-negative mutant KCNK9, responsible for the disease, and electrophysiological experiments demonstrated that ion channel function was involved in the migration defect. Calcium imaging revealed that KCNK9 knockdown or expression of dominant-negative mutant KCNK9 increased the fraction of neurons showing calcium transients and the frequency of spontaneous calcium transients. Mislocated neurons seen after KCNK9 knockdown stayed in the deep cortical layers, showing delayed morphological maturation. Taken together, our results suggest that dysfunction of KCNK9 causes a migration defect in the cortex via an activity-dependent mechanism.

Diabetes is associated with increased risk of diastolic dysfunction, heart failure, QT prolongation and rhythm disturbances independent of age, hypertension or coronary artery disease. Although these observations suggest electrical remodeling in the heart with diabetes, the relationship between the metabolic and the functional derangements is poorly understood. Exploiting a mouse model (MHC-PPAR alpha) with cardiac-specific overexpression of the peroxisome proliferator-activated receptor alpha (PPAR(x), a key driver of diabetes-related lipid metabolic dysregulation, the experiments here were aimed at examining directly the link(s) between alterations in cardiac fatty acid metabolism and the functioning of repolarizing, voltage-gated K+ (Kv) channels. Electrophysiological experiments on left (LV) and right (RV) ventricular myocytes isolated from young (5-6 week) MHC-PPAR alpha mice revealed marked K current remodeling: I-to/f densities are significantly (P < 0.01) lower, whereas 4,, densities are significantly (P<0.001) higher in MHC-PPAR alpha, compared with age-matched wild type (WT), LV and RV myocytes. Consistent with the observed reductions in I-to/f density, expression of the KCND2 (Kv4.2) transcript is significantly (P<0.001) lower in MHC-PPARa., compared with WT, ventricles. Western blot analyses revealed that expression of the Kv accessory protein, KChIP2, is also reduced in MHC-PPARa ventricles in parallel with the decrease in Kv4.2. Although the properties of the endogenous and the "augmented" I-ss suggest a role(s) for two pore domain K+ channel (K2P) pore-forming subunits, the expression levels of KCNK2 (TREK1), KCNK3 (TASK1) and KCNK5 (TASK2) in MHC-PPAR alpha and WT ventricles are not significantly different. The molecular mechanisms underlying I-to/f and I-ss remodeling in MHC-PPAR alpha. ventricular myocytes, therefore, are distinct. (c) 2008 Elsevier Inc. All rights reserved.