Cell type–specific spatial and functional coupling between mammalian brain Kv2.1 K+ channels and ryanodine receptors

The Kv2.1 voltage‐gated K⁺ channel is widely expressed throughout mammalian brain, where it contributes to dynamic activity‐dependent regulation of intrinsic neuronal excitability. Here we show that somatic plasma membrane Kv2.1 clusters are juxtaposed to clusters of intracellular ryanodine receptor (RyR) Ca²⁺‐release channels in mouse brain neurons, most prominently in medium spiny neurons (MSNs) of the striatum. Electron microscopy–immunogold labeling shows that in MSNs, plasma membrane Kv2.1 clusters are adjacent to subsurface cisternae, placing Kv2.1 in close proximity to sites of RyR‐mediated Ca²⁺ release. Immunofluorescence labeling in transgenic mice expressing green fluorescent protein in specific MSN populations reveals the most prominent juxtaposed Kv2.1:RyR clusters in indirect pathway MSNs. Kv2.1 in both direct and indirect pathway MSNs exhibits markedly lower levels of labeling with phosphospecific antibodies directed against the S453, S563, and S603 phosphorylation site compared with levels observed in neocortical neurons, although labeling for Kv2.1 phosphorylation at S563 was significantly lower in indirect pathway MSNs compared with those in the direct pathway. Finally, acute stimulation of RyRs in heterologous cells causes a rapid hyperpolarizing shift in the voltage dependence of activation of Kv2.1, typical of Ca²⁺/calcineurin‐dependent Kv2.1 dephosphorylation. Together, these studies reveal that striatal MSNs are distinct in their expression of clustered Kv2.1 at plasma membrane sites juxtaposed to intracellular RyRs, as well as in Kv2.1 phosphorylation state. Differences in Kv2.1 expression and phosphorylation between MSNs in direct and indirect pathways provide a cell‐ and circuit‐specific mechanism for coupling intracellular Ca²⁺ release to phosphorylation‐dependent regulation of Kv2.1 to dynamically impact intrinsic excitability. J. Comp. Neurol. 522:3555–3574, 2014. © 2014 Wiley Periodicals, Inc.     

Long-term results of slow pathway ablation in patients with atrioventricular nodal reentrant tachycardia: simple approach

AimsThe aim of this study was to report the short- and long-term results of slow pathway radiofrequency (RF) ablation in patients with atrioventricular (AV) nodal reentrant tachycardia (AVNRT) using a simplified approach (2 catheters and short applications of RF).Materials and MethodsThis was a retrospective study that included consecutive patients with AVNRT. We used an anatomical approach with only 2 catheters. Decremental AV nodal conduction and atrial-His conduction interval jump were measured. To detect the onset of the QRS, we used surface lead II. During the stimulation protocol, we performed S2-QRS and S3-QRS measurements. An increase in the S3-QRS3 interval of 50 milliseconds or greater in response to a decrease in the S2-QRS2 coupling interval of 10 milliseconds was defined as a discontinuous AV nodal function curve and taken as evidence of dual antegrade AV pathways. Atrioventricular nodal reentrant tachycardia was demonstrated by the presence of dual AV nodal physiology, atrial echoes, and tachycardia induction with a 1:1 AV relationship and a VA interval of less than 70 milliseconds. Short RF applications (10-15 seconds) were delivered at an intermediate point between the posteroseptal and medioseptal regions of the Koch triangle. The applications were considered effective when junctional rhythm appeared. The end point was the demonstration of slow pathway modification without AVNRT induction.ResultsThree hundred forty-four patients (age, 49.22 ± 17.47 years; 254 were female) were included. Discontinuous AV nodal function curves were found in 271 patients (78.77%), and short-term success was achieved in all patients. The anterograde jump in AV nodal conduction was abolished after RF in 222 patients (81.91%), and discontinuous AV nodal conduction and single AV nodal echo beats persisted in 49 cases (18%). The mean number of RF application was 7.79 ± 2.23, the mean number of effective applications was 4.63 ± 0.62, and the mean RF application time was 54.92 ± 8.03 seconds. The total procedure and fluoroscopy time was 29.45 ± 9.6 and 10.87 ± 2.36 minutes, respectively. After the procedure, all patients were followed up for a mean of 46.44 ± 18.89 months, and 7 patients (2%) presented AVNRT recurrences. Complications were observed in 4 patients (1.16%); no permanent AV block was observed.ConclusionIn this study, slow pathway RF ablation using a simplified approach technique is an effective and safe approach for the treatment of AVNRT.     

Prevalence of diabetes mellitus and impaired glucose regulation in Spain: the Di@bet.es Study

Aims/hypothesis

The Di@bet.es Study is the first national study in Spain to examine the prevalence of diabetes and impaired glucose regulation.

Methods

A population-based, cross-sectional, cluster sampling study was carried out, with target population being the entire Spanish population. Five thousand and seventy-two participants in 100 clusters (health centres or the equivalent in each region) were randomly selected with a probability proportional to population size. Participation rate was 55.8%. Study variables were a clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, BMI, waist and hip circumference, blood pressure) and OGTT (75?g).

Results

Almost 30% of the study population had some carbohydrate disturbance. The overall prevalence of diabetes mellitus adjusted for age and sex was 13.8% (95% CI 12.8, 14.7%), of which about half had unknown diabetes: 6.0% (95% CI 5.4, 6.7%). The age- and sex-adjusted prevalence rates of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IFG?CIGT were 3.4% (95% CI 2.9, 4.0%), 9.2% (95% CI 8.2, 10.2%) and 2.2% (95% CI 1.7, 2.7%), respectively. The prevalence of diabetes and impaired glucose regulation increased significantly with age (p?p?Conclusions/interpretation The Di@bet.es Study shows, for the first time, the prevalence rates of diabetes and impaired glucose regulation in a representative sample of the Spanish population.