Sex‐specific activation of SK current by isoproterenol facilitates action potential triangulation and arrhythmogenesis in rabbit ventricles

Sex has a large influence on cardiac electrophysiological properties. Whether sex differences exist in apamin‐sensitive small conductance Ca2+‐activated K+ (SK) current (IKAS) remains unknown. We performed optical mapping, transmembrane potential, patch clamp, western blot and immunostaining in 62 normal rabbit ventricles, including 32 females and 30 males. IKAS blockade by apamin only minimally prolonged action potential (AP) duration (APD) in the basal condition for both sexes, but significantly prolonged APD in the presence of isoproterenol in females. Apamin prolonged APD at the level of 25% repolarization (APD25) more prominently than APD at the level of 80% repolarization (APD80), consequently reversing isoproterenol‐induced AP triangulation in females. In comparison, apamin prolonged APD to a significantly lesser extent in males and failed to restore the AP plateau during isoproterenol infusion. IKAS in males did not respond to the L‐type calcium current agonist BayK8644, but was amplified by the casein kinase 2 (CK2) inhibitor 4,5,6,7‐tetrabromobenzotriazole. In addition, whole‐cell outward IKAS densities in ventricular cardiomyocytes were significantly larger in females than in males. SK channel subtype 2 (SK2) protein expression was higher and the CK2/SK2 ratio was lower in females than in males. IKAS activation in females induced negative intracellular Ca2+–voltage coupling, promoted electromechanically discordant phase 2 repolarization alternans and facilitated ventricular fibrillation (VF). Apamin eliminated the negative Ca2+–voltage coupling, attenuated alternans and reduced VF inducibility, phase singularities and dominant frequencies in females, but not in males. We conclude that β‐adrenergic stimulation activates ventricular IKAS in females to a much greater extent than in males. IKAS activation plays an important role in ventricular arrhythmogenesis in females during sympathetic stimulation

Understanding PITX2-Dependent Atrial Fibrillation Mechanisms through Computational Models

From MDPI via Jisc Publications RouterHistory: accepted 2021-07-16, pub-electronic 2021-07-19Publication status: PublishedFunder: National Key Research and Development Program of China; Grant(s): 2019YFC0120100, 2019YFC0121907Funder: National Natural Science Foundation of China; Grant(s): 61901192Atrial fibrillation (AF) is a common arrhythmia. Better prevention and treatment of AF are needed to reduce AF-associated morbidity and mortality. Several major mechanisms cause AF in patients, including genetic predispositions to AF development. Genome-wide association studies have identified a number of genetic variants in association with AF populations, with the strongest hits clustering on chromosome 4q25, close to the gene for the homeobox transcription PITX2. Because of the inherent complexity of the human heart, experimental and basic research is insufficient for understanding the functional impacts of PITX2 variants on AF. Linking PITX2 properties to ion channels, cells, tissues, atriums and the whole heart, computational models provide a supplementary tool for achieving a quantitative understanding of the functional role of PITX2 in remodelling atrial structure and function to predispose to AF. It is hoped that computational approaches incorporating all we know about PITX2-related structural and electrical remodelling would provide better understanding into its proarrhythmic effects leading to development of improved anti-AF therapies. In the present review, we discuss advances in atrial modelling and focus on the mechanistic links between PITX2 and AF. Challenges in applying models for improving patient health are described, as well as a summary of future perspectives

Concomitant SK current activation and sodium current inhibition cause J wave syndrome

The mechanisms of J wave syndrome (JWS) are incompletely understood. Here, we showed that the concomitant activation of small-conductance calcium-activated potassium (SK) current (IKAS) and inhibition of sodium current by cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) recapitulate the phenotypes of JWS in Langendorff-perfused rabbit hearts. CyPPA induced significant J wave elevation and frequent spontaneous ventricular fibrillation (SVF), as well as sinus bradycardia, atrioventricular block, and intraventricular conduction delay. IKAS activation by CyPPA resulted in heterogeneous shortening of action potential (AP) duration (APD) and repolarization alternans. CyPPA inhibited cardiac sodium current (INa) and decelerated AP upstroke and intracellular calcium transient. SVFs were typically triggered by short-coupled premature ventricular contractions, initiated with phase 2 reentry and originated more frequently from the right than the left ventricles. Subsequent IKAS blockade by apamin reduced J wave elevation and eliminated SVF. β-Adrenergic stimulation was antiarrhythmic in CyPPA-induced electrical storm. Like CyPPA, hypothermia (32.0°C) also induced J wave elevation and SVF. It facilitated negative calcium-voltage coupling and phase 2 repolarization alternans with spatial and electromechanical discordance, which were ameliorated by apamin. These findings suggest that IKAS activation contributes to the development of JWS in rabbit ventricles

Chromaticity and Optical Properties of Colored and Black Solar-Thermal Absorbing Coatings

Two important trends in solar thermal utilization in buildings are building integration and color appearance. Coatings based on titanium alloy nitride show variety of different colors. These can be controlled by film thickness for a single layer stack, or by putting another layer on top of the first layer. Strong absorption around 500 nm is important to cause color appearance. Chromaticity and optical properties of colored coatings were studied and compared to black coatings. In the three-point gamut system, such colors show an additive mixture property. Solar absorptance of 0.80 to 0.95 can be obtained with thermal emittance of 0.04 to 0.09 (100oC). These coatings provide a choice for solar thermal integration in buildings where appearance is an important feature

"Trusteeship for an estate"

Mantojuma aizgādnības institūta būtība ir radīt efektīvu mehānismu, kas nodrošinātu pilvērtīgu mantojuma darbību līdz brīdim, kamēr mantinieki tiek apstiprināti mantojuma tiesībās. Tā mērķis ir nodrošināt mantojuma saglabāšanu. Lai gan normatīvajos aktos nesen tika veikti grozījumi, kas paredz mantojuma aizgādnības funkciju veikt zvērinātiem notāriem, nevis tiesai, tādējādi paātrinot šo procesu, regulējums vēl joprojām ir smagnējs un laikietilpīgs. Bakalaura darba mērķis ir izpētīt normatīvajos aktos veiktos grozījumus, konstatēt esošos problēmjautājums un rast iespējamos risinājums, kas nodrošinātu mantojuma aizgādnības institūta realizēšanu atbilstoši tā mērķim. Darba izstrādes gaitā tiek pētīti un analizēti normatīvie akti, tiesu nolēmumi, kā arī tiek veiktas konsultācijas ar nozaru speciālistiem. Bakalaura darba ietvaros autore piedāvā grozīt un papildināt spēkā esošo regulējumu, kas ievērojami atvieglotu mantojuma aizgādnības institūta pielietošanu. Atslēgvārdi: mantojuma aizgādnība, mantojuma aizgādnis, mantojuma pārstāvība, mantojuma apsardzība, mantojums, mantojuma masa, zvērināts notārs, bāriņtiesa.Trusteeship of an estate institute point of matter is to create an effective mechanism, to ensure full estate activity until heirs are approved under inheritance law. The aim of it is to ensure keeping estate. Although laws and regulations recently have been amended, which provides trusteeship of estate function to manage sworn notaries, not a court, thus speeding the process up. The regulation is still heavy and time consuming. Aim of the bachelor thesis is to explore amendments in law, establish existing issues and find possible solutions, which provides trusteeship of an estate institute implementation according to its purpose. In course of developing paper, are studied and analyzed regulatory enactments, court judgments, as well as are caried out the consultations with experts of this field. In framework of bachelor thesis the author offers to amend and improve existing law in force, which considerably would relieve trusteeship of an estate insitute usability. Keywords: trusteeship of an estate, trustee of an estate, representation of an estate, protection of an estate, estate, entirety of property of an estate, notary public, orphan’s court

The influence of oxygen in TiAlOxNy on the optical properties of colored solar-absorbing coatings

Low cost and ease of fabrication are important factors for solar-thermal applications in energy-efficient buildings. This contribution reports the influence of oxygen on structure, optical properties and chromaticity of TiAlOxNy thin films prepared by DC magnetron sputtering. It is an extension of a previous study on colored solar-thermal absorbers based on titanium-aluminum nitride. The purpose is to investigate the possibility of using TiAlOxNy as middle layer to achieve a gradient effect. The results reveal that the structure and optical properties of the TiAlOxNy coatings are sensitive to the oxygen content under certain sputtering conditions.  The ratio of oxygen/nitrogen of 0.7:10 is the most appropriate to form the crystalline structure of TiAlON.  The optical constants of TiAlN and TiAlON were deduced by fitting the experimental data. It shows that both the refractive index (n) and the extinction coefficient (k) are decreased when oxygen is introduced to form titanium-aluminium nitro-oxide. The gradient effect can be achieved and controlled by adjusting the ratio of oxygen/nitrogen flow during the process to enhance solar absorptance while keeping the desired color appearance