Treatment of atrial fibrillation with doxapram: TASK-1 potassium channel inhibition as a novel pharmacological strategy.

Aims: TASK-1 (K2P3.1) two-pore-domain potassium channels are atrial-specific and significantly up-regulated in atrial fibrillation (AF) patients, contributing to AF-related electrical remodelling. Inhibition of TASK-1 in cardiomyocytes of AF patients was shown to counteract AF-related action potential duration shortening.

Temporal Relations between Cortical Network Oscillations and Breathing Frequency during REM Sleep.

Nasal breathing generates a rhythmic signal which entrains cortical network oscillations in widespread brain regions on a cycle-to-cycle time scale. It is unknown, however, how respiration and neuronal network activity interact on a larger time scale: are breathing frequency and typical neuronal oscillation patterns correlated? Is there any directionality or temporal relationship? To address these questions, we recorded field potentials from the posterior parietal cortex of mice together with respiration during REM sleep. In this state, the parietal cortex exhibits prominent θ and γ oscillations while behavioral activity is minimal, reducing confounding signals.

Identification of a critical binding site for local anaesthetics in the side pockets of K 1 channels.

Background And Purpose: Local anaesthetics block sodium and a variety of potassium channels. Although previous studies identified a residue in the pore signature sequence together with three residues in the S6 segment as a putative binding site, the precise molecular basis of inhibition of K channels by local anaesthetics remained unknown. Crystal structures of K channels predict that some of these residues point away from the central cavity and face into a drug binding site called side pockets.

Optogenetic tools for manipulation of cyclic nucleotides functionally coupled to cyclic nucleotide-gated channels.

Background And Purpose: The cyclic nucleotides cAMP and cGMP are ubiquitous second messengers regulating numerous biological processes. Malfunctional cNMP signalling is linked to diseases and thus is an important target in pharmaceutical research. The existing optogenetic toolbox in Caenorhabditis elegans is restricted to soluble adenylyl cyclases, the membrane-bound Blastocladiella emersonii CyclOp and hyperpolarizing rhodopsins; yet missing are membrane-bound photoactivatable adenylyl cyclases and hyperpolarizers based on K currents.

Molecular Pharmacology of K Potassium Channels.

Potassium channels of the tandem of two-pore-domain (K) family were among the last potassium channels cloned. However, recent progress in understanding their physiological relevance and molecular pharmacology revealed their therapeutic potential and thus these channels evolved as major drug targets against a large variety of diseases. However, after the initial cloning of the fifteen family members there was a lack of potent and/or selective modulators.

Recent advances in cochlear hair cell nanophysiology: subcellular compartmentalization of electrical signaling in compact sensory cells.

In recent years, genetics, physiology, and structural biology have advanced into the molecular details of the sensory physiology of auditory hair cells. Inner hair cells (IHCs) and outer hair cells (OHCs) mediate two key functions: active amplification and non-linear compression of cochlear vibrations by OHCs and sound encoding by IHCs at their afferent synapses with the spiral ganglion neurons. OHCs and IHCs share some molecular physiology, e.

Systemic Oxidative Stress, Aging and the Risk of Cardiovascular Events in the General Female Population.

Menopause is associated with increased cardiovascular risk, in which oxidative stress plays a pivotal role. Systemic oxidative stress is reflected by decreased levels of free thiols (R-SH, sulfhydryl groups), which are key components of the extracellular antioxidant machinery. In this study, we investigated the relation between serum free thiols as marker of oxidative stress and the female cardiovascular phenotype, as well as potential associations with the risk of cardiovascular (CV) events in pre- and postmenopausal women from the general population.

Epigenetic regulation of cardiac electrophysiology in atrial fibrillation: HDAC2 determines action potential duration and suppresses NRSF in cardiomyocytes.

Atrial fibrillation (AF) is associated with electrical remodeling, leading to cellular electrophysiological dysfunction and arrhythmia perpetuation. Emerging evidence suggests a key role for epigenetic mechanisms in the regulation of ion channel expression. Histone deacetylases (HDACs) control gene expression through deacetylation of histone proteins.

Integrated information theory does not make plant consciousness more convincing.

It has been proposed by some plant scientists that plants are cognitive and conscious organisms, although this is a minority view. Here we present a brief summary of some of the arguments against this view, followed by a critique of an article in this same issue of Biochemical and Biophysical Research Communications by Calvo, Baluska, and Trewavas (2020) that cites Integrated Information Theory (IIT) as providing additional support for plant consciousness. The authors base their argument on the assumptions that all cells are conscious and that consciousness is confined to life.

Acid sphingomyelinase promotes SGK1-dependent vascular calcification.

In chronic kidney disease (CKD), hyperphosphatemia is a key factor promoting medial vascular calcification, a common complication associated with cardiovascular events and high mortality. Vascular calcification involves osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs), but the complex signaling events inducing pro-calcific pathways are incompletely understood. The present study investigated the role of acid sphingomyelinase (ASM)/ceramide as regulator of VSMC calcification.

Inflammation: a putative link between phosphate metabolism and cardiovascular disease.

Dietary habits in the western world lead to increasing phosphate intake. Under physiological conditions, extraosseous precipitation of phosphate with calcium is prevented by a mineral buffering system composed of calcification inhibitors and tight control of serum phosphate levels. The coordinated hormonal regulation of serum phosphate involves fibroblast growth factor 23 (FGF23), αKlotho, parathyroid hormone (PTH) and calcitriol.

NO Synthesis Markers are Not Significantly Associated with Blood Pressure and Endothelial Dysfunction in Patients with Arterial Hypertension: A Cross-Sectional Study.

Nitric oxide (NO) synthesis markers, comprising L-homoarginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), are significantly associated with cardiovascular events and mortality. Being involved in NO pathways, they may be of high importance regulating vascular tone and arterial hypertension, but data on this topic are sparse and controversial. In this study, we evaluated whether these NO synthesis markers are associated with blood pressure values and pulse wave velocity (PWV).

New Cav1.2 Channelopathy with High-Functioning Autism, Affective Disorder, Severe Dental Enamel Defects, a Short QT Interval, and a Novel Loss-Of-Function Mutation.

Complex neuropsychiatric-cardiac syndromes can be genetically determined. For the first time, the authors present a syndromal form of short QT syndrome in a 34-year-old German male patient with extracardiac features with predominant psychiatric manifestation, namely a severe form of secondary high-functioning autism spectrum disorder (ASD), along with affective and psychotic exacerbations, and severe dental enamel defects (with rapid wearing off his teeth) due to a heterozygous loss-of-function mutation in the gene (NM_000719.6: c.

Debunking a myth: plant consciousness.

Claims that plants have conscious experiences have increased in recent years and have received wide coverage, from the popular media to scientific journals. Such claims are misleading and have the potential to misdirect funding and governmental policy decisions. After defining basic, primary consciousness, we provide new arguments against 12 core claims made by the proponents of plant consciousness.

Safety and Tolerability of Sodium Thiosulfate in Patients with an Acute Coronary Syndrome Undergoing Coronary Angiography: A Dose-Escalation Safety Pilot Study (SAFE-ACS).

Background: In animal studies, hydrogen sulfide (HS) has been shown to protect the heart from ischemia-reperfusion injury. This study evaluates the safety and tolerability of the HS donor sodium thiosulfate (STS) in patients with acute coronary syndrome (ACS).

Methods: Eighteen patients, undergoing coronary angiography for ACS, received STS intravenously immediately after arrival at the catheterization laboratory according to a "3 + 3 dose-escalation design" with fixed dosing endpoint (0, 2.

Role of SGK1 in the Osteogenic Transdifferentiation and Calcification of Vascular Smooth Muscle Cells Promoted by Hyperglycemic Conditions.

In diabetes mellitus, hyperglycemia promotes the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) to enhance medial vascular calcification, a common complication strongly associated with cardiovascular disease and mortality. The mechanisms involved are, however, still poorly understood. Therefore, the present study explored the potential role of serum- and glucocorticoid-inducible kinase 1 (SGK1) during vascular calcification promoted by hyperglycemic conditions.

Alterations of distributed neuronal network oscillations during acute pain in freely-moving mice.

The experience of pain involves the activation of multiple brain areas. Pain-specific activity patterns within and between these local networks remain, however, largely unknown. We measured neuronal network oscillations in different relevant regions of the mouse brain during acute pain, induced by subcutaneous injection of capsaicin into the left hind paw.

VEGF-D Downregulation in CA1 Pyramidal Neurons Exerts Asymmetric Changes of Dendritic Morphology without Correlated Electrophysiological Alterations.

The morphology of dendritic arbors determines the location, strength and interaction of synaptic inputs. It is therefore important to understand the factors regulating dendritic arborization both during development and in situations of physiological or pathological plasticity. We have recently shown that VEGF-D (Vascular Endothelial Growth Factor D) is required to maintain length and complexity of basal dendrites in mouse hippocampal pyramidal cells.

Associations of Thyroid Hormones and Resting Heart Rate in Patients Referred to Coronary Angiography.

Resting heart rate (RHR) is associated with increased risk of cardiovascular morbidity and mortality. Thyroid hormones exert several effects on the cardiovascular system, but the relation between thyroid function and RHR remains to be further established. We evaluated whether measures of thyroid hormone status are associated with RHR in patients referred to coronary angiography.

Anesthetics and plants: no pain, no brain, and therefore no consciousness.

Plants have a rich variety of interactions with their environment, including adaptive responses mediated by electrical signaling. This has prompted claims that information processing in plants is similar to that in animals and, hence, that plants are conscious, intelligent organisms. In several recent reports, the facts that general anesthetics cause plants to lose their sensory responses and behaviors have been taken as support for such beliefs.

Elevated serum magnesium lowers calcification propensity in Memo1-deficient mice.

MEdiator of cell MOtility1 (MEMO1) is a ubiquitously expressed redox protein involved in extracellular ligand-induced cell signaling. We previously reported that inducible whole-body Memo1 KO (cKO) mice displayed a syndrome of premature aging and disturbed mineral metabolism partially recapitulating the phenotype observed in Klotho or Fgf23-deficient mouse models. Here, we aimed at delineating the contribution of systemic mineral load on the Memo1 cKO mouse phenotype.

Oxidative Stress and Redox-Modulating Therapeutics in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is associated with the production of reactive species that target cysteine redox switches in proteins, thereby affecting gene regulation, DNA damage, ion transport, intermediary metabolism, and mitochondrial function. Precursors of reactive species are derived from organic and inorganic compounds and their cofactors, including amino acids, vitamins, oxygen, nitrite, and sulfate. Nutrition and the gut microbiome fuel this process to a significant extent.