Caveolar targeting links Kv1.3 with the insulin-dependent adipocyte physiology.

The voltage-dependent potassium channel Kv1.3 participates in peripheral insulin sensitivity. Genetic ablation of Kv1.3 triggers resistance to diet-induced weight gain, thereby pointing to this protein as a pharmacological target for obesity and associated type II diabetes. However, this role is under intense debate because Kv1.3 expression in adipose tissue raises controversy. We demonstrated that Kv1.3 is expressed in white adipose tissue from humans and rodents. Moreover, other channels, such as Kv1.1, Kv1.2, Kv1.4 and especially Kv1.5, from the same Shaker family are also present. Although elevated insulin levels and adipogenesis remodel the Kv phenotype, which could lead to multiple heteromeric complexes, Kv1.3 markedly participates in the insulin-dependent regulation of glucose uptake in mature adipocytes. Adipocyte differentiation increased the expression of Kv1.3, which is targeted to caveolae by molecular interactions with caveolin 1. Using a caveolin 1-deficient 3T3-L1 adipocyte cell line, we demonstrated that the localization of Kv1.3 in caveolar raft structures is important for proper insulin signaling. Insulin-dependent phosphorylation of the channel occurs at the onset of insulin-mediated signaling. However, when Kv1.3 was spatially outside of these lipid microdomains, impaired phosphorylation was exhibited. Our data shed light on the putative role of Kv1.3 in weight gain and insulin-dependent responses contributing to knowledge about adipocyte physiology.

Autotransplantation of human carotid body cell aggregates for treatment of Parkinson's disease.

OBJECTIVE: In this study, we assessed the feasibility of autotransplantation of carotid body (CB) cell aggregates into the striatum for the treatment of patients with Parkinson's disease (PD). METHODS: Six patients with advanced PD underwent bilateral autotransplantation of CB cell aggregates into the striatum. They were evaluated clinically preoperatively and for 18 months after surgery according to the recommendations of the Core Assessment Program for Intracerebral Transplantation. RESULTS: No major complications or adverse events resulted from the cell implantation or surgical procedures. During the course of the study, there was no significant aggravation of dyskinesia or decline in cognitive function in any of the patients. Five of the six patients who underwent transplantation manifested a measurable degree of clinical improvement evidenced by standardized clinical rating scales for PD. A decrease in the blinded Unified Parkinson's Disease Rating Scale Part III in the "off" state, the main measure of transplant efficacy in our study, was found to be maximal (between 26 and 74%) at 6 months after surgery. At 1 year, clear reductions in the blinded Unified Parkinson's Disease Rating Scale Part III were maintained in three patients (24, 38, and 52%, respectively). Modest improvement was seen in two patients (13 and 17%), and the sole patient who showed no improvement had the most fibrosis in the CB. The age of the patient and the state of the CB tissue were adversely correlated with clinical improvement after CB autotransplantation. CONCLUSION: This pilot study indicates that CB autograft transplantation is a relatively simple, safe, and viable therapeutical approach for the treatment of patients with advanced PD. More studies are needed to optimize the procedure and to assess its general applicability for the treatment of patients with PD.

Gap junctions in developing neocortex: a review.

Several independent lines of evidence indicate that gap junctional coupling is widespread and functionally important in early cortical development. The extensive expression of many connexins, the clusters of coupled neuroblasts or neurons revealed by tracer injections or the functional coactivation of neurons shown by calcium imaging can be seen as pieces of the same puzzle. At the same time, there is a lack of electrophysiological experiments at early developmental stages that directly demonstrate coupling between pairs of cells. The function of this gap junctional coupling is still mysterious, though it may be involved in controlling neurogenesis, differentiation or the formation of columnar microcircuits.