Cantú syndrome (CS) is caused by the gain of function mutations in the and genes encoding, respectively, for the sulfonylureas receptor type 2 (SUR2) and the inwardly rectifier potassium channel 6.1 (Kir6.1) of the ATP-sensitive potassium (KATP) channels.
View Article and Find Full Text PDFWe present the first structure of the human Kir2.1 channel containing both transmembrane domain (TMD) and cytoplasmic domain (CTD). Kir2.
View Article and Find Full Text PDFBisphosphonates (BPs) are the most used bone-specific anti-resorptive agents, often chosen as first-line therapy in several bone diseases characterized by an imbalance between osteoblast-mediated bone production and osteoclast-mediated bone resorption. BPs target the farnesyl pyrophosphate synthase (FPPS) in osteoclasts, reducing bone resorption. Lately, there has been an increasing interest in BPs direct pro-survival/pro-mineralizing properties in osteoblasts and their pain-relieving effects.
View Article and Find Full Text PDFATP-sensitive potassium (K-ATP) channels are ubiquitously expressed on the plasma membrane of cells in several organs, including the heart, pancreas, and brain, and they govern a wide range of physiological processes. In pancreatic β-cells, K-ATP channels composed of Kir6.2 and SUR1 play a key role in coupling blood glucose and insulin secretion.
View Article and Find Full Text PDFZoledronic acid (ZOL) is used as a bone-specific antiresorptive drug with antimyeloma effects. Adverse drug reactions (A.D.
View Article and Find Full Text PDF(1) Background: Cantu syndrome (CS) arises from gain-of-function (GOF) mutations in the and genes, which encode ATP-sensitive K (KATP) channel subunits SUR2 and Kir6.1, respectively. Most CS patients have mutations in SUR2, the major component of skeletal muscle KATP, but the consequences of SUR2 GOF in skeletal muscle are unknown.
View Article and Find Full Text PDFIn this study, we investigated the dynamics and functional characteristics of the KirBac3.1 S129R, a mutated bacterial potassium channel for which the inner pore-lining helix (TM2) was engineered so that the bundle crossing is trapped in an open conformation. The structure of this channel has been previously determined at high atomic resolution.
View Article and Find Full Text PDFCNS Neurol Disord Drug Targets
March 2022
Arachidonic acids and its metabolites modulate plenty of ligand-gated, voltage-dependent ion channels, and metabolically regulated potassium channels including ATP-sensitive potassium channels (KATP). KATP channels are hetero-multimeric complexes of sulfonylureas receptors (SUR1, SUR2A or SUR2B) and the pore-forming subunits (Kir6.1 and Kir6.
View Article and Find Full Text PDFCantù syndrome (CS) arises from mutations in and genes that lead to gain of function (GOF) of ATP-sensitive potassium (KATP) channels containing SUR2A and Kir6.1 subunits, respectively, of KATP channels. Pathological consequences of CS have been reported for cardiac and smooth muscle cells but consequences in skeletal muscle are unknown.
View Article and Find Full Text PDFThe efficacy of minoxidil (MXD) ethanolic solutions (1%-5% w/v) in the treatment of androgenetic alopecia is limited by adverse reactions. The toxicological effects of repeated topical applications of escalating dose (0.035%-3.
View Article and Find Full Text PDFBisphosphonates (BPs) reduce bone pain and fractures by balancing the osteoblast/osteoclast ratio. The behavior of ion channels in the presence of BPs is not known. To investigate this, the effect of zoledronic acid BP (ZOL) (3 × 10 to 5 × 10 M) treatment, on ion channels, cell proliferation, and mineralization, has been investigated on preosteoclast-like cells, RAW264.
View Article and Find Full Text PDFBisphosphonates such as zoledronic, alendronic and risedronic acids are a class of drugs clinically used to prevent bone density loss and osteoporosis. Novel P-C-P bisphosphonates were synthesized for targeting human farnesyl pyrophosphate synthase (hFPPS) and human geranylgeranyl pyrophosphate synthase (hGGPPS), key enzymes of the mevalonate pathway, and capable of anti-proliferative action on a number of cell lines (PC3, MG63, MC3T3, RAW 264.7, J774A.
View Article and Find Full Text PDFThe effects of Ca-activated K⁺ (BK) channel modulation by Paxilline (PAX) (10⁻10 M), Iberiotoxin (IbTX) (0.1⁻1 × 10 M) and Resveratrol (RESV) (1⁻2 × 10 M) on cell cycle and proliferation, AKT1p phosphorylation, cell diameter, and BK currents were investigated in SH-SY5Y cells using Operetta-high-content-Imaging-System, ELISA-assay, impedentiometric counting method and patch-clamp technique, respectively. IbTX (4 × 10 M), PAX (5 × 10 M) and RESV (10 M) caused a maximal decrease of the outward K⁺ current at +30 mV (Vm) of -38.
View Article and Find Full Text PDFObjective: We aimed to investigate in a clinical setting, the effects of different classes of psychotropic drugs on cardiac electrophysiological measures linked with an increased risk of sudden cardiac death.
Methods: We conducted a cross-sectional study in a population of 1059 psychiatric inpatients studying the effects of various psychotropic drugs on the T-peak to T-end (TpTe) interval, QT dispersion and QT interval.
Results: Methadone use showed a strong association with TpTe prolongation (odds ratio (OR)=12.
Objectives: We tested the noninferiority of a fast-track rule-out protocol for the diagnosis of non-ST-segment elevation myocardial infarction vs noncoronary chest pain based on the single-sampling combined assessment of medium-sensitivity cardiac troponin I and ultra-sensitive copeptin compared with the serial assessment of medium-sensitivity cardiac troponin I.
Methods: Ultra-sensitive copeptin and medium-sensitivity cardiac troponin I levels were measured at presentation in 196 consecutive patients admitted to the emergency department for acute nontraumatic chest pain within 6 hours from symptoms onset and without ST-segment elevation on a 12-lead electrocardiogram. The diagnostic performance for non-ST-segment elevation myocardial infarction diagnosis of the dual-marker single-sampling strategy with medium-sensitivity cardiac troponin I and ultra-sensitive copeptin on admission was compared with that of the serial 0- and 3-hour medium-sensitivity cardiac troponin I sampling in reference to the adjudicated postdischarge diagnosis, using both the comparison of area under the curve (AUC) receiver operating characteristic and the McNemar chi-square test.