Schwarzcantrell3538

25 to 9.38% (P = 0.030), 84.38 to 62.50% (P = 0.048) and 46.88 to 21.88% (P = 0.035), respectively. The high dose of UTI significantly postponed the occurrence of DCS (P = 0.030) and prolonged survival time (P = 0.009) compared with the Saline group, and significantly ameliorated inflammation responses, endothelial injuries and oxidative damage. The results strongly suggest the benefit of UTI on DCS, especially for severe cases. Large doses are needed to achieve significant effects. UTI may be a potential ideal pharmacological candidate for the treatment of severe DCS. Copyright © 2020 Meng, Qing, Li, Zhang, Yi, Zhao and Xu.The transient receptor potential vanilloid member 1 (TRPV1) in the central nervous system may contribute to homeostatic plasticity by regulating intracellular Ca2+, which becomes unbalanced in age-related neurodegenerative diseases, including Alzheimer's and Huntington's. Glaucomatous optic neuropathy - the world's leading cause of irreversible blindness - involves progressive degeneration of retinal ganglion cell (RGC) axons in the optic nerve through sensitivity to stress related to intraocular pressure (IOP). In models of glaucoma, genetic deletion of TRPV1 (Trpv1-/- ) accelerates RGC axonopathy in the optic projection, whereas TRPV1 activation modulates RGC membrane polarization. In continuation of these studies, here, we found that Trpv1-/- increases the compound action potential (CAP) of optic nerves subjected to short-term elevations in IOP. This IOP-induced increase in CAP was not directly due to TRPV1 channels in the optic nerve, because the TRPV1-selective antagonist iodoresiniferatoxin had no effect on the CAP for wild-type optic nerve. Rather, the enhanced CAP in Trpv1-/- optic nerve was associated with increased expression of the voltage-gated sodium channel subunit 1.6 (NaV1.6) in longer nodes of Ranvier within RGC axons, rendering Trpv1-/- optic nerve relatively insensitive to NaV1.6 antagonism via 4,9-anhydrotetrodotoxin. These results indicate that with short-term elevations in IOP, Trpv1-/- increases axon excitability through greater NaV1.6 localization within longer nodes. In neurodegenerative disease, native TRPV1 may tune NaV expression in neurons under stress to match excitability to available metabolic resources. Copyright © 2020 McGrady, Risner, Vest and Calkins.Rapid firing from pulmonary veins (PVs) frequently initiates atrial fibrillation, which is a common comorbidity associated with hypertension, heart failure, and valvular disease, i.e., conditions that pathologically increase cardiomyocyte stretch. Autonomic tone plays a crucial role in PV arrhythmogenesis, while its interplay with myocardium stretch remains uncertain. Two-microelectrode technique was used to characterize electrophysiological response of Wistar rat PV to adrenaline at baseline and under mild (150 mg of applied weight that corresponds to a pulmonary venous pressure of 1 mmHg) and moderate (10 g, ∼26 mmHg) stretch. Low concentrations of adrenaline (25-100 nmol/L) depolarized the resting membrane potential selectively within distal PV (by 26 ± 2 mV at baseline, by 18 ± 1 mV at 150 mg, P less then 0.001, and by 5.9 ± 1.1 mV at 10 g, P less then 0.01) suppressing action potential amplitude and resulting in intra-PV conduction dissociation and rare episodes of spontaneous activity (arrhythmia index of 0.4 ± 0.2, NS vs. no activity at baseline). In contrast, 1-10 μmol/L of adrenaline recovered intra-PV propagation. While mild stretch did not affect PV electrophysiology at baseline, moderate stretch depolarized the resting potential within distal PV (-56 ± 2 mV vs. -82 ± 1 mV at baseline, P less then 0.01), facilitated the triggering of rapid PV firing by adrenaline (arrhythmia index 4.4 ± 0.2 vs. 1.3 ± 0.4 in unstretched, P less then 0.001, and 1.7 ± 0.8 in mildly stretched preparations, P less then 0.005, at 10 μmol/L adrenaline) and induced frequent episodes of potentially arrhythmogenic atrial "echo" extra beats. Our findings demonstrate complex interactions between the sympathetic tone and mechanical stretch in the development of arrhythmogenic activity within PVs that may impact an increased atrial fibrillation vulnerability in patients with elevated blood pressure. Copyright © 2020 Egorov, Rosenshtraukh and Glukhov.A major challenge for all organisms that live in temperate and subpolar regions is to adapt physiology and activity to different photoperiods. A long-standing model assumes that there are morning (M) and evening (E) oscillators with different photoreceptive properties that couple to dawn and dusk, respectively, and by this way adjust activity to the different photoperiods. click here In the fruit fly Drosophila melanogaster, M and E oscillators have been localized to specific circadian clock neurons in the brain. Here, we investigate under different photoperiods the activity pattern of flies expressing the clock protein PERIOD (PER) only in subsets of M and E oscillators. We found that all fly lines that expressed PER only in subsets of the clock neurons had difficulties to track the morning and evening in a wild-type manner. The lack of the E oscillators advanced M activity under short days, whereas the lack of the M oscillators delayed E activity under the same conditions. In addition, we found that flies expressing PER only in subsets of clock neurons showed higher activity levels at certain times of day or night, suggesting that M and E clock neurons might inhibit activity at specific moments throughout the 24 h. Altogether, we show that the proper interaction between all clock cells is important for adapting the flies' activity to different photoperiods and discuss our findings in the light of the current literature. Copyright © 2020 Menegazzi, Beer, Grebler, Schlichting, Schubert and Helfrich-Förster.Non-excitable cells (NECs) such as cardiac myofibroblasts that are electrotonically coupled to cardiomyocytes affect conduction velocity (θ) by representing a capacitive load (CL increased membrane to be charged) and a resistive load (RL partial depolarization of coupled cardiomyocytes). In this study, we untangled the relative contributions of both loading modalities to NEC-dependent arrhythmogenic conduction slowing. Discrimination between CL and RL was achieved by reversibly removing the RL component by light activation of the halorhodopsin-based hyperpolarizing membrane voltage actuator eNpHR3.0-eYFP (enhanced yellow fluorescent protein) expressed in communication-competent fibroblast-like NIH3T3 cells (3T3 HR cells) that served as a model of coupled NECs. Experiments were conducted with strands of neonatal rat ventricular cardiomyocytes coated at increasing densities with 3T3 HR cells. Impulse conduction along preparations stimulated at 2.5 Hz was assessed with multielectrode arrays. The relative density of 3T3 HR cells was determined by dividing the area showing eYFP fluorescence by the area covered with cardiomyocytes [coverage factor (CF)].