Fine-tuning pH sensor H98 by remote essential residues in the hydrogen-bond network of mTASK-3.

TASK-3 generates a background K conductance which when inhibited by acidification depolarizes membrane potential and increases cell excitability. These channels sense pH by protonation of histidine residue H98, but recent evidence revealed that several other amino acid residues also contribute to TASK-3 pH sensitivity, suggesting that the pH sensitivity is determined by an intermolecular network. Here we use electrophysiology and molecular modeling to characterize the nature and requisite role(s) of multiple amino acids in pH sensing by TASK-3.

Painful diabetic neuropathy: The role of ion channels.

Painful diabetic neuropathy (PDN) is a common chronic complication of diabetes that causes neuropathic pain and negatively affects the quality of life. The management of PDN is far from satisfactory. At present, interventions are primarily focused on symptomatic treatment.

Deciphering the Molecular Mechanism of Escin against Neuropathic Pain: A Network Pharmacology Study.

Background: Escin is the main active component in . It has been demonstrated that escin has anti-inflammatory properties. This study combined the methods of network pharmacology, molecular docking, and molecular dynamics to explore the molecular mechanism of escin against neuropathic pain (NP).

Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic Targets.

TWIK-related acid-sensitive K (TASK) channels, including TASK-1, TASK-3, and TASK-5, are important members of the two-pore domain potassium (K) channel family. TASK-5 is not functionally expressed in the recombinant system. TASK channels are very sensitive to changes in extracellular pH and are active during all membrane potential periods.

Putative Roles of Astrocytes in General Anesthesia.

General anesthetics are a mainstay of modern medicine, and although much progress has been made towards identifying molecular targets of anesthetics and neural networks contributing to endpoints of general anesthesia, our understanding of how anesthetics work remains unclear. Reducing this knowledge gap is of fundamental importance to prevent unwanted and life-threatening side-effects associated with general anesthesia. General anesthetics are chemically diverse, yet they all have similar behavioral endpoints, and so for decades, research has sought to identify a single underlying mechanism to explain how anesthetics work.

Dorsal penile nerve block alleviates pain in men undergoing rigid cystoscopy: A single-center, randomized, double-blind, and placebo-controlled trial.

Objective: To assess the effectiveness and safety of dorsal penile nerve block (DPNB) compared with tetracaine gel in analgesia for men undergoing rigid cystoscopy.

Patients And Methods: This study was conducted as a prospective, randomized, double-blind, placebo-controlled, and single-center trial. Men undergoing diagnostic rigid cystoscopy were randomly allocated into one of three groups (n = 86 each): (1) tetracaine gel group (DPNB with saline), (2) DPNB group (DPNB with ropivacaine + plain lubricant), and (3) combination group (DPNB with ropivacaine + tetracaine gel).

Isoflurane inhibits a Kir4.1/5.1-like conductance in neonatal rat brainstem astrocytes and recombinant Kir4.1/5.1 channels in a heterologous expression system.

All inhalation anesthetics used clinically including isoflurane can suppress breathing; since this unwanted side effect can persist during the postoperative period and complicate patient recovery, there is a need to better understand how isoflurane affects cellular and molecular elements of respiratory control. Considering that astrocytes in a brainstem region known as the retrotrapezoid nucleus (RTN) contribute to the regulation of breathing in response to changes in CO/H (i.e.

Injection of D1 receptor antagonist SCH23390 into the periaqueductal gray attenuates morphine withdrawal symptoms in rats.

The aim of this study was to investigate the relationship of dopamine D1 receptor (D1R) and its downstream factors with morphine withdrawal symptoms in rats. Rats were injected intraperitoneally with morphine in a dose-escalating manner. The midbrain periaqueductal gray (PAG) area was microinjected with D1R antagonist SCH23390 or D1R agonist SKF38393.

Sevoflurane- and propofol-based regimens show comparable effect on oxygenation in patients undergoing cardiac valve replacement with cardiopulmonary bypass.

Background: Our study aimed to compare the effects of Sevoflurane- and propofol-based anaesthetic regimens on oxygenation during the early period of cardiopulmonary bypass (CPB) in patients undergoing cardiac valve-replacement surgery.

Methods: Patients undergoing mechanical mitral, aortic or double valve replacement were enrolled and randomly divided into two groups: the sevoflurane-based anaesthetic regimen group consisted of patients who received 1-3% sevoflurane inhalation during anaesthesia maintenance and the propofol-based anaesthetic regimen group consisted of patients who received 6-10 mg/kg/h of propofol infusion during anaesthesia maintenance. The partial pressure of oxygen/fraction of inspired oxygen (PaO/FiO), respiratory mechanics and haemodynamics were recorded during CPB.

Amelioration of postoperative cognitive dysfunction in mice by mesenchymal stem cell-conditioned medium treatments is associated with reduced inflammation, oxidative stress and increased BDNF expression in brain tissues.

Objective: Mesenchymal stem cells (MSCs) are widely used in regeneration and repair of various tissues and organs, and whether MSC-conditioned medium (MSC-CM) has protective effects in postoperative cognitive dysfunction (POCD) remains largely unknown. We aimed to assess the therapeutic effect and explore the mechanisms of MSC-CM therapy in a POCD mouse model.

Methods: Sixty C57BL/6 mice were randomly assigned to 3 groups: control, POCD and POCD + MSC-CM.

Sevoflurane Posttreatment Attenuates Lung Injury Induced by Oleic Acid in Dogs.

Background: In animal models, both sevoflurane and propofol protect against acute lung injury (ALI), especially when administered prior to ALI onset. We hypothesized that when compared to propofol, sevoflurane administration after the onset of acute respiratory distress syndrome would mitigate oleic acid (OA)-induced ALI in dogs.

Methods: Dogs were randomly assigned to receive intravenous OA to induce ALI (n = 7 for each OA group) or saline as an OA control (n = 6 for each control).

Establishment of An Alloxan-induced Diabetes Model in Daphnia Pulex.

Objective To establish a Daphnia model of alloxan-induced diabetes. Methods Daphnia were exposed to three different concentrations of alloxan (3, 5, and 10 mmol/L) for 30 minutes. Blood glucose and survival rate were recorded for 72 hours after alloxan insult.

[Effects of Etomidate on mRNA Expression of Ion Channels in Daphnia Pulex].

Ion channels are involved in the mechanism of anesthetic action and side effect.The transcription and expression of ion channel genes can be modulated by general anesthetics.The adverse effect of continuous infusion of etomidate has been concerned.

Ethanol alters the expression of ion channel genes in Daphnia pulex.

Background: Heavy drinking can increase heart rate and blood glucose, induce hypoxic tolerance, impair brain cognitive functions, and alter gene expressions. These phenomena may occur even in response to small dose of ethanol exposure or during its withdrawal.

Objectives: To evaluate whether persistent low concentrations of ethanol exposure affect organism function and the gene expressions of ion channels.

Dorsal penile nerve block for rigid cystoscopy in men: study protocol for a randomized controlled trial.

Background: Pain is common in men undergoing rigid cystoscopy. Even with the application of a lubricant containing 2 % lidocaine, about 76 % of men suffer from mild to severe pain when undergoing rigid cystoscopy. The most painful part of the procedure for men is when the cystoscope passes through the membranous urethra.

TASK Channels on Basal Forebrain Cholinergic Neurons Modulate Electrocortical Signatures of Arousal by Histamine.

Unlabelled: Basal forebrain cholinergic neurons are the main source of cortical acetylcholine, and their activation by histamine elicits cortical arousal. TWIK-like acid-sensitive K(+) (TASK) channels modulate neuronal excitability and are expressed on basal forebrain cholinergic neurons, but the role of TASK channels in the histamine-basal forebrain cholinergic arousal circuit is unknown. We first expressed TASK channel subunits and histamine Type 1 receptors in HEK cells.

Coagulopathy associated with cell salvage transfusion following cerebrovascular surgery.

A 35-year-old man was scheduled for dural arteriovenous fistula resection for vascular malformation under general anesthesia and a cell saver device was employed. The patient suffered from massive bleeding for the rupture of arteriovenous malformations from the beginning of the operation and 1000 mL cell-saved blood was transfused. After autologous blood transfusion and fluid resuscitation, blood oozed significantly from the surgical wounds, and the administration of cryoprecipitate and fibrinogen has no effect.

Evaluation of the antinociceptive effects of lidocaine and bupivacaine on the tail nerves of healthy rats.

This study was designed to develop a simple and effective model of tail nerve block without general anaesthesia and surgical incision, to assist in exploring and studying new local anaesthetics. Tail nerves of adult, male Sprague-Dawley rats were blocked by injecting 1% lidocaine and 0.5% bupivacaine, respectively.

TASK Channel Deletion Reduces Sensitivity to Local Anesthetic-induced Seizures.

Background: Local anesthetics (LAs) are typically used for regional anesthesia but can be given systemically to mitigate postoperative pain, supplement general anesthesia, or prevent cardiac arrhythmias. However, systemic application or inadvertent intravenous injection can be associated with substantial toxicity, including seizure induction. The molecular basis for this toxic action remains unclear.

Isoflurane pre-treatment before cardiopulmonary bypass alleviates neutrophil accumulation in dog lungs.

Objective: This study investigated the effect of isoflurane pretreatment on cardiopulmonary bypass (CPB)-related lung injury.

Methods: Twelve dogs were randomly divided into two groups of six each. In one group, 1.

Emulsified isoflurane preconditioning protects against liver and lung injury in rat model of hemorrhagic shock.

Background: Isoflurane has demonstrated protective effects against ischemia/reperfusion injury in some organs. In this study, using the hemorrhagic shock model, we investigated whether emulsified isoflurane preconditioning protected against liver and lung injury caused by massive surgical blood loss.

Methods: Male Sprague-Dawley (SD) rats were randomly divided into five groups: a control group, a hemorrhagic shock (HS) group, an intralipid (IL) group, an isoflurane (Iso) group, and an emulsified isoflurane (E-Iso) group.

An altered TH1/TH2 and pro-inflammatory cytokine profile in patients with end-stage renal disease detected by suspension array technology.

Background: Patients with end-stage renal disease (ESRD) have an impaired immune response with a dysregulated Th1/Th2 cytokine network.

Methods: Twelve ESRD patients on HD were enrolled, and their data of cytokines alterations were divided into pre- and post-HD groups, while data from 12 healthy volunteers served as control. Th1/Th2 and pro-inflammatory cytokines were all measured by suspension array (SA) technology with interleukin (IL)-8 detected simultaneously by ELISA.