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PubMed Journals Articles About "Inhibition Hyperpolarization Activated Cyclic Nucleotide Gated Channels Beta" RSS

07:53 EDT 21st March 2019 | BioPortfolio

Inhibition Hyperpolarization Activated Cyclic Nucleotide Gated Channels Beta PubMed articles on BioPortfolio. Our PubMed references draw on over 21 million records from the medical literature. Here you can see the latest Inhibition Hyperpolarization Activated Cyclic Nucleotide Gated Channels Beta articles that have been published worldwide.

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Showing "Inhibition hyperpolarization activated cyclic nucleotide gated channels beta" PubMed Articles 1–25 of 13,000+

Inhibition of hyperpolarization-activated cyclic nucleotide-gated channels by beta-blocker carvedilol.

Carvedilol is a clinically broadly used and effective beta-blocker for treatment of congestive heart failure (CHF) and several clinical trials have demonstrated that carvedilol shows a favourable effect compared to other beta-blocking agents in patients with CHF. The mechanism underlying the advantage of carvedilol over other beta-blocking agents is not clearly understood. In addition to beta-blockers, inhibitors of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which play a critical ro...


Hyperpolarization-activated and cyclic nucleotide-gated channel proteins as emerging new targets in neuropathic pain.

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels are activated during hyperpolarization, and there is an inward flow of current, which is termed as hyperpolarization-activated current, Ih. Initially, these channels were identified on the pacemaker cells of the heart. Nowadays, these are identified on different regions of the nervous system, including peripheral nerves, dorsal root ganglia, dorsal horns, and different parts of the brain. There are four different types of HCN channels (H...

Hyperpolarization-activated cyclic nucleotide-gated channels contribute to spontaneous activity in L4 C-fiber nociceptors, but not Aβ-non-nociceptors, after axotomy of L5-spinal nerve in the rat in vivo: Erratum.


Acupoint sensitization is associated with increased excitability and hyperpolarization-activated current (I) in C- but not Aδ-type neurons.

Under pathological conditions, acupoint sensitization is the phenomenon of acupoints transforming from the stable state to the dynamic state. Evidences suggest that hyperpolarization-activated current (I), conducted by the hyperpolarization-activated/cyclic nucleotide-gated (HCN) channel, greatly contributes to the peripheral and central sensitization. However, the role of the I current in acupoint sensitization has not been explained. In the present study, changes in excitability, I density and the HCN cha...

Loss of HCN1 subunits causes absence epilepsy in rats.

Hyperpolarized-activated cyclic nucleotide-gated (HCN) channels underlie hyperpolarization-activated current (Ih) and are involved in controlling the excitability and electrical responsiveness of neurons. Absence epilepsy is clinically defined by a sudden, brief impairment of consciousness and behavioral arrest. Spike-and-wave discharges (SWDs) on electroencephalograms (EEG) are a diagnostic hallmark of absence epilepsy. In rat models of absence epilepsy, impaired function or expression of HCN1, a subtype o...

In Vitro Analyses of Novel HCN4 Gene Mutations.

The hyperpolarization-activated cyclic nucleotide-gated cation channel HCN4 contributes significantly to the generation of basic cardiac electrical activity in the sinus node and is a mediator of modulation by β-adrenergic stimulation. Heterologous expression of sick sinus syndrome (SSS) and bradycardia associated mutations within the human HCN4 gene results in altered channel function. The main aim was to describe the functional characterization of three (two novel and one known) missense mutations of HCN...

Targeting light-gated chloride channels to neuronal somatodendritic domain reduces their excitatory effect in the axon.

Light-gated chloride channels are emerging as promising optogenetic tools for inhibition of neural activity. However, their effects depend on the transmembrane chloride electrochemical gradient and may be complex due to the heterogeneity of this gradient in different developmental stages, neuronal types, and subcellular compartments. Here we characterized a light-gated chloride channel, GtACR2, in mouse cortical neurons. We found that GtACR2 activation inhibited the soma, but unexpectedly depolarized the pr...

A comparison of the ability of Leu- and Pro-oxytocin to regulate intracellular Ca and Ca-activated K channels at human and marmoset oxytocin receptors.

The neurohypophyseal hormone oxytocin (OT) regulates biological functions in both peripheral tissues and the central nervous system (CNS). In the CNS, OT influences social processes including peer relationships, maternal-infant bonding and affiliative social relationships. In mammals, the nonapeptide OT structure is highly conserved with leucine in the 8th position (Leu-OT). In marmosets () a nonsynonymous nucleotide substitution in the gene codes for proline in the 8th residue position (Pro-OT). OT binds ...

Identification and characterization of a series of novel HCN channel inhibitors.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a critical role in controlling pacemaker activity in both heart and nervous system. Developing HCN channel inhibitors has been proposed to be an important strategy for the treatment of pain, heart failure, arrhythmias, and epilepsy. One HCN channel inhibitor, ivabradine, has been clinically approved for the treatment of angina pectoris and heart failure. In this study, we designed and synthesized eight alkanol amine derivatives, and ass...

Mode of action of piperovatine, an insecticidal piperamide isolated from Piper piscatorum (Piperaceae), against voltage-gated sodium channels.

Piperamides, which are secondary metabolites in the genus Piper, have potent insecticidal activity, and have thus inspired the development of novel insecticides. In this study, piperovatine, a piperamide from Piper piscatorum (Piperaceae), was investigated using a two-electrode voltage clamp to clarify its detailed mode of action against voltage-gated sodium channels, a classic target. In Xenopus oocytes expressing voltage-gated sodium channels from German cockroach (Blattella germanica), piperovatine induc...

Pre-synaptic sympathetic calcium channels, cyclic nucleotide-coupled phosphodiesterases and cardiac excitability.

In sympathetic neurons innervating the heart, action potentials activate voltage-gated Ca channels and evoke Ca entry into presynaptic terminals triggering neurotransmitter release. Binding of transmitters to specific receptors stimulates signal transduction pathways that cause changes in cardiac function. The mechanisms contributing to presynaptic Ca dynamics involve regulation of endogenous Ca buffers, in particular the endoplasmic reticulum, mitochondria and cyclic nucleotide targeted pathways. The purpo...

HCN4 Gene Variations in Sudden Unexplained Nocturnal Death Syndrome in the Southern Han Chinese Population.

Sudden unexplained nocturnal death syndrome (SUNDS) is widely considered to be related to hereditary fatal arrhythmias. Hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) channels are widely distributed in sinus myocytes and play a profound role in generating pacemaker electro-activity in cardiomyocytes. In the present study, the potential correlation between HCN4 gene variations and the occurrence of SUNDS was investigated. Genomic DNA was extracted from blood samples of both 119 unrelate...

Electrophysiological Identification and Activity Analyses of Plasma Membrane K+ Channels in Maize Guard Cells.

Stomatal movement, which plays an essential role in plant transpiration and photosynthesis, is controlled by ion channels that mediate K+ and anion fluxes across the plasma membrane (PM) of guard cells. These channels in dicots are accurately regulated by various physiological factors, such as pH, ABA, and Ca2+; however, the data in monocots are limited. Here the whole-cell patch-clamping technique was applied to analyze the properties and regulations of PM K+ channels in maize guard cells. The results indi...

Potassium Channels in Vascular Smooth Muscle: A Pathophysiological and Pharmacological Perspective.

Potassium (K ) ion channel activity is an important determinant of vascular tone by regulating cell membrane potential (MP). Activation of K channels leads to membrane hyperpolarization and subsequently vasodilatation, while inhibition of the channels causes membrane depolarization and then vasoconstriction. So far five distinct types of K channels have been identified in vascular smooth muscle cells (VSMCs); Ca -activated K channels (BK ), voltage-dependent K channels (K ), ATP-sensitive K channels (K ), i...

Mammalian skeletal muscle does not express functional voltage-gated H channels.

High metabolic activity and existence of a large transmembrane inward electrochemical gradient for H at rest promote intracellular acidification of skeletal muscle. Exchangers and cotransports efficiently contend against accumulation of intracellular H and associated deleterious effects on muscle functions. Voltage-gated H channels have also been found to represent another H extrusion pathway in cultured muscle cells. Up to now, the skeletal muscle cell was therefore the unique vertebrate excitable cell in ...

Regulation of BK Channels by Beta and Gamma Subunits.

Ca- and voltage-gated K channels of large conductance (BK channels) are expressed in a diverse variety of both excitable and inexcitable cells, with functional properties presumably uniquely calibrated for the cells in which they are found. Although some diversity in BK channel function, localization, and regulation apparently arises from cell-specific alternative splice variants of the single pore-forming α subunit ( KCa1.1, Kcnma1, Slo1) gene, two families of regulatory subunits, β and γ, define BK cha...

Luteolin-induced coronary arterial relaxation involves activation of the myocyte voltage-gated K channels and inward rectifier K channels.

Luteolin has been shown to be beneficial to cardiovascular tissues and organs. We aimed to study its vasospasmolytic effects against various vasoconstrictors in the isolated rat coronary arteries (RCAs) and its electrophysiological effects on K currents via voltage-gated potassium (Kv) channels and inward rectifier potassium (Kir) channels in freshly isolated rat coronary arterial smooth muscle cells (RCASMCs).

The role of the C-terminus of SUR in the differential regulation of β-cell and cardiac K channels by MgADP and metabolism.

β-cell K channels are partially open in the absence of metabolic substrates, whereas cardiac K channels are closed. Using cloned channels heterologously expressed in Xenopus oocytes we measured the effect of MgADP on the MgATP concentration-inhibition curve immediately after patch excision. MgADP caused a far more striking reduction in ATP inhibition of Kir6.2/SUR1 then Kir6.2/SUR2A channels; an effect that declined rapidly after patch excision. Exchanging the final 42 amino acids of SUR was sufficient to ...

Phosphodiesterase 1 Bridges Glutamate Inputs with NO- and Dopamine-Induced Cyclic Nucleotide Signals in the Striatum.

The calcium-regulated phosphodiesterase 1 (PDE1) family is highly expressed in the brain, but its functional role in neurones is poorly understood. Using the selective PDE1 inhibitor Lu AF64196 and biosensors for cyclic nucleotides including a novel biosensor for cGMP, we analyzed the effect of PDE1 on cAMP and cGMP in individual neurones in brain slices from male newborn mice. Release of caged NMDA triggered a transient increase of intracellular calcium, which was associated with a decrease in cAMP and cGM...

Dynamic compartmentalization of calcium channel signalling in neurons.

Calcium fluxes through the neuronal membrane are strictly limited in time due to biophysical properties of voltage-gated and ligand-activated ion channels and receptors. Being embedded into the crowded dynamic environment of biological membranes, Ca-permeable receptors and channels undergo perpetual spatial rearrangement, which enables their temporary association and formation of transient signalling complexes. Thus, efficient calcium-mediated signal transduction requires mechanisms to support very precise ...

The Hyperpolarization-Activated HCN4 Channel is Important for Proper Maintenance of Oscillatory Activity in the Thalamocortical System.

Hyperpolarization-activated cation channels are involved, among other functions, in learning and memory, control of synaptic transmission and epileptogenesis. The importance of the HCN1 and HCN2 isoforms for brain function has been demonstrated, while the role of HCN4, the third major neuronal HCN subunit, is not known. Here we show that HCN4 is essential for oscillatory activity in the thalamocortical (TC) network. HCN4 is selectively expressed in various thalamic nuclei, excluding the thalamic reticular n...

Inhibitory effect of immunosuppressive drug tacrolimus on voltage-gated K current in rabbit coronary arterial smooth muscle cells.

In the present study, we investigated the inhibitory effect of tacrolimus, a macrolide immunosuppressive drug that acts through calcineurin inhibition, on voltage-gated K (Kv) channels expressed in native smooth muscle cells isolated from the coronary arteries of rabbits. Tacrolimus reduced the amplitude of Kv currents in a dose-dependent manner with an IC value and Hill coefficient of 7.80 ± 3.01μM and 1.07 ± 0.25, respectively. Tacrolimus caused a shift in the activation curve toward a more positive po...

The Functional Role of Protease-Activated Receptors on Contractile Responses by Activation of Ca Sensitization Pathways in Simian Colonic Muscles.

It has been known that activation of protease-activated receptors (PAR) affects gastrointestinal motility. In this study, we tested the effects of PAR agonists on electrical and contractile responses, and Ca sensitization pathways in simian colonic muscles. The Simian colonic muscle was initially hyperpolarized by PAR agonists. After the transient hyperpolarization, simian colonic muscle repolarized to the control resting membrane potential (RMP) without a delayed depolarization. Apamin significantly reduce...

Circadian pacemaker neurons of the Madeira cockroach are inhibited and activated by GABA and GABA receptors.

GABA is the most abundant neurotransmitter in the circadian pacemaker circuits of mammals and insects. In the Madeira cockroach the accessory medulla (AME) in the brain's optic lobes is the circadian clock that orchestrates rest-activity rhythms in synchrony with light dark cycles. Three prominent GABAergic tracts connect the AME to termination sites of compound eye photoreceptors in the lamina and medulla. Parallel GABAergic light entrainment pathways were suggested to either advance or delay the clock for...

Histamine causes influx via T-type voltage-gated calcium channels in an enterochromaffin tumor cell line: potential therapeutic target in adverse food reactions.

The P-STS human ileal neuroendocrine tumor cells, as a model for gut enterochromaffin cells, are strongly and synergistically activated by histamine plus acetylcholine (ACh), presumably via histamine 4 receptors, and weakly activated by histamine alone. Sensing these signals, enterochromaffin cells could participate in intestinal intolerance or allergic reactions to food constituents associated with elevated histamine levels. In this study we aimed to analyze the underlying molecular mechanisms. Inhibition ...


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