Catecholamine-Induced Inflammasome Activation in the Heart Following Photothrombotic Stroke.

Cerebrovascular stroke patients exhibit an increased incidence of cardiac arrhythmias. The pathomechanisms underlying post-traumatic cardiac dysfunction include a surge of catecholamines and an increased systemic inflammatory response, but whether inflammasome activation contributes to cardiac dysfunction remains unexplored. Here, we used a mouse model of photothrombotic stroke (PTS) to investigate the role of inflammasome activation in post-stroke cardiac dysfunction by catecholamines and to evaluate the effectiveness of the inflammasome inhibitor IC100 on inflammasome activation.

PUFA stabilizes a conductive state of the selectivity filter in IKs channels.

In cardiomyocytes, the KCNQ1/KCNE1 channel complex mediates the slow delayed-rectifier current (IKs), pivotal during the repolarization phase of the ventricular action potential. Mutations in IKs cause long QT syndrome (LQTS), a syndrome with a prolonged QT interval on the ECG, which increases the risk of ventricular arrhythmia and sudden cardiac death. One potential therapeutical intervention for LQTS is based on targeting IKs channels to restore channel function and/or the physiological QT interval.

Lipophilic compounds restore function to neurodevelopmental-associated KCNQ3 mutations.

A major driver of neuronal hyperexcitability is dysfunction of K channels, including voltage-gated KCNQ2/3 channels. Their hyperpolarized midpoint of activation and slow activation and deactivation kinetics produce a current that regulates membrane potential and impedes repetitive firing. Inherited mutations in KCNQ2 and KCNQ3 are linked to a wide spectrum of neurodevelopmental disorders (NDDs), ranging from benign familial neonatal seizures to severe epileptic encephalopathies and autism spectrum disorders.

Pharmacological Screening of Kv7.1 and Kv7.1/KCNE1 Activators as Potential Antiarrhythmic Drugs in the Zebrafish Heart.

Long QT syndrome (LQTS) can lead to ventricular arrhythmia and sudden cardiac death. The most common congenital cause of LQTS is mutations in the channel subunits generating the cardiac potassium current . Zebrafish () have been proposed as a powerful system to model human cardiac diseases due to the similar electrical properties of the zebrafish heart and the human heart.

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.

K1.5-Kβ1.3 Recycling Is PKC-Dependent.

K1.5 channel function is modified by different regulatory subunits. Kβ1.

The unconventional biogenesis of Kv7.1-KCNE1 complexes.

The potassium channel Kv7.1 associates with the KCNE1 regulatory subunit to trigger cardiac currents. Although the Kv7.

Polyunsaturated fatty acid analogues differentially affect cardiac Na, Ca, and K channels through unique mechanisms.

The cardiac ventricular action potential depends on several voltage-gated ion channels, including Na, Ca, and K channels. Mutations in these channels can cause Long QT Syndrome (LQTS) which increases the risk for ventricular fibrillation and sudden cardiac death. Polyunsaturated fatty acids (PUFAs) have emerged as potential therapeutics for LQTS because they are modulators of voltage-gated ion channels.

Activation of K 7 channels as a novel mechanism for NO/cGMP-induced pulmonary vasodilation.

Background And Purpose: The NO/cGMP pathway represents a major physiological signalling controlling tone in pulmonary arteries (PA), and drugs activating this pathway are used to treat pulmonary arterial hypertension. K channels expressed in PA smooth muscle cells (PASMCs) are key determinants of vascular tone. We aimed to analyse the contribution of K 1.

D242N, a K7.1 LQTS mutation uncovers a key residue for I voltage dependence.

K7.1 and KCNE1 co-assemble to give rise to the I current, one of the most important repolarizing currents of the cardiac action potential. Its relevance is underscored by the identification of >500 mutations in K7.

Fludarabine Inhibits K1.3 Currents in Human B Lymphocytes.

Fludarabine (F-ara-A) is a purine analog commonly used in the treatment of indolent B cell malignancies that interferes with different aspects of DNA and RNA synthesis. K1.3 K channels are membrane proteins involved in the maintenance of K homeostasis and the resting potential of the cell, thus controlling signaling events, proliferation and apoptosis in lymphocytes.

In-Depth Study of the Interaction, Sensitivity, and Gating Modulation by PUFAs on K Channels; Interaction and New Targets.

Voltage gated potassium channels (K) are membrane proteins that allow selective flow of K ions in a voltage-dependent manner. These channels play an important role in several excitable cells as neurons, cardiomyocytes, and vascular smooth muscle. Over the last 20 years, it has been shown that omega-3 polyunsaturated fatty acids (PUFAs) enhance or decrease the activity of several cardiac K channels.

Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease.

Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection.

A new KCNQ1 mutation at the S5 segment that impairs its association with KCNE1 is responsible for short QT syndrome.

Aims: KCNQ1 and KCNE1 encode Kv7.1 and KCNE1, respectively, the pore-forming and the accessory subunits of the slow delayed rectifier potassium current, IKs. KCNQ1 mutations are associated with long and short QT syndrome.

Marine n-3 PUFAs modulate IKs gating, channel expression, and location in membrane microdomains.

Aims: Polyunsaturated fatty n-3 acids (PUFAs) have been reported to exhibit antiarrhythmic properties. However, the mechanisms of action remain unclear. We studied the electrophysiological effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on IKs, and on the expression and location of Kv7.

Functional assembly of Kv7.1/Kv7.5 channels with emerging properties on vascular muscle physiology.

Objective: Voltage-dependent K(+) (Kv) channels from the Kv7 family are expressed in blood vessels and contribute to cardiovascular physiology. Although Kv7 channel blockers trigger muscle contractions, Kv7 activators act as vasorelaxants. Kv7.

Modulation of voltage-dependent and inward rectifier potassium channels by 15-epi-lipoxin-A4 in activated murine macrophages: implications in innate immunity.

Potassium channels modulate macrophage physiology. Blockade of voltage-dependent potassium channels (Kv) by specific antagonists decreases macrophage cytokine production and inhibits proliferation. In the presence of aspirin, acetylated cyclooxygenase-2 loses the activity required to synthesize PGs but maintains the oxygenase activity to produce 15R-HETE from arachidonate.

Polyunsaturated Fatty acids modify the gating of kv channels.

Polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic properties, which are attributed to their capability to modulate ion channels. This PUFAs ability has been reported to be due to their effects on the gating properties of ion channels. In the present review, we will focus on the role of PUFAs on the gating of two Kv channels, Kv1.

Effects of n-3 Polyunsaturated Fatty Acids on Cardiac Ion Channels.

Dietary n-3 polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic properties, and these effects have been attributed to their capability to modulate ion channels. In the present review, we will focus on the effects of PUFAs on a cardiac sodium channel (Na(v)1.5) and two potassium channels involved in cardiac atrial and ventricular repolarization (K(v)) (K(v)1.

Stereoselective interactions between local anesthetics and ion channels.

Local anesthetics are useful probes of ion channel function and structure. Stereoselective interactions are especially interesting because they can reveal three-dimensional relationships between drugs and channels with otherwise identical biophysical and physicochemical properties. Furthermore, stereoselectivity suggests direct and specific receptor-mediated action, and identification of such stereospecific interactions may have important clinical consequences.

A framework for assessment and monitoring of arthropods in a lowland tropical forest.

By applying principles of adaptive management, and by using the valuable information that arthropods provide from assessment and monitoring programs, managers can identify and reduce possible impacts on biodiversity in development projects. In 1996, the Smithsonian Institution's Monitoring and Assessment of Biodiversity program worked together with Shell Prospecting and Development Peru to establish an adaptive management program to protect biodiversity in a natural gas exploration project in a Peruvian rainforest. In this paper, we outlined the conceptual steps involved in establishing an assessment and monitoring program for arthropods, including setting objectives, evaluating the results and making decisions.