Melatonin inhibits voltage-gated potassium K4.2 channels and negatively regulates melatonin secretion in rat pineal glands.

Melatonin is synthesized in and secreted from the pineal glands and regulates circadian rhythms. Although melatonin has been reported to modulate the activity of ion channels in several tissues, its effects on pineal ion channels remain unclear. In the present study, the effects of melatonin on voltage-gated K (K) channels, which play a role in regulating the resting membrane potential, were examined in rat pinealocytes.

Up-regulated expression of two-pore domain K channels, KCNK1 and KCNK2, is involved in the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary arterial hypertension.

Background: Pulmonary arterial hypertension (PAH) is a severe and rare disease in the cardiopulmonary system. Its pathogenesis involves vascular remodeling of the pulmonary artery, which results in progressive increases in pulmonary arterial pressure. Chronically increased pulmonary arterial pressure causes right ventricular hypertrophy and subsequent right heart failure.

Hypothermia Attenuates Neurotoxic Microglial Activation via TRPV4.

Therapeutic hypothermia (TH) provides neuroprotection. However, the cellular mechanisms underlying the neuroprotective effects of TH are not fully elucidated. Regulation of microglial activation has the potential to treat a variety of nervous system diseases.

Caveolin-1 forms a complex with P2X7 receptor and tunes P2X7-mediated ATP signaling in mouse bone marrow-derived macrophages.

The ionotropic purinergic P2X7 receptor responds to extracellular ATP and can trigger proinflammatory immune signaling in macrophages. Caveolin-1 (Cav-1) is known to modulate functions of macrophages and innate immunity. However, it is unknown how Cav-1 modulates P2X7 receptor activity in macrophages.

Pimaric acid reduces vasoconstriction via BK channel activation and VDCC inhibition in rat pulmonary arterial smooth muscles.

Pulmonary vessels play a pivotal role in oxygen circulation. We previously demonstrated that pimaric acid (PiMA) activated large-conductance Ca-activated K (BK) channels and inhibited voltage-dependent Ca channels (VDCCs). In the present study, PiMA attenuated vasoconstriction induced by high K or endothelin-1 in rat pulmonary arterial smooth muscles (PASMs).

New screw technique for posterior column and ischial fixation from the anterior approach for acetabular fractures.

Management of the ischial fragment in acetabular fractures is a considerable problem. In this report, we presented how to drill or screw around the posterior column and ischium from the anterior approach using a novel 'sleeve guide technique' and the difficulty of plating. A sleeve, drill, depth gauge and driver from DepuySynthes were prepared.

Corosolic acid ameliorates vascular remodeling in pulmonary arterial hypertension via the downregulation of STAT3 signaling.

Pulmonary arterial hypertension (PAH) is a progressive and fatal disease that is characterized by vascular remodeling of the pulmonary artery. PAH remodeling is primarily caused by the excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs). Therefore, an inhibitory mechanism is expected as a target for the treatment of PAH.

Mitofusin 1 and 2 differentially regulate mitochondrial function underlying Ca signaling and proliferation in rat aortic smooth muscle cells.

Mitochondria play a substantial role in cytosolic Ca buffering and energy metabolism. We recently demonstrated that mitofusin 2 (Mfn2) regulated Ca signaling by tethering mitochondria and sarcoplasmic reticulum (SR), and thus, facilitated mitochondrial function and the proliferation of vascular smooth muscle cells (VSMCs). However, the physiological role of mitofusin 1 (Mfn1) on Ca signaling and mitochondrial function remains unclear.

A 75-year history of microplastic fragment accumulation rates in a semi-enclosed hypoxic basin.

Plastic budgets in the marine environment and their long-term trends are yet to be fully understood. Measuring the accumulation rates in bottom sediments is crucial to solving the riddle of missing ocean plastics. Previous studies based on coastal sediment cores have found that accumulation rates have increased with increases in plastic production and/or regional populations.

Local Ca Signals within Caveolae Cause Nuclear Translocation of CaMK1α in Mouse Vascular Smooth Muscle Cells.

An increase in intracellular Ca concentration ([Ca]) activates Ca-sensitive enzymes such as Ca/calmodulin-dependent kinases (CaMK) and induces gene transcription in various types of cells. This signaling pathway is called excitation-transcription (E-T) coupling. Recently, we have revealed that a L-type Ca channel/CaMK kinase (CaMKK) 2/CaMK1α complex located within caveolae in vascular smooth muscle cells (SMCs) can convert [Ca] changes to gene transcription profiles that are related to chemotaxis.

Upregulated ClC3 Channels/Transporters Elicit Swelling-Activated Cl Currents and Induce Excessive Cell Proliferation in Idiopathic Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling of the pulmonary artery, which is mainly attributed to the excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) comprising the medial layer of pulmonary arteries. The activity of ion channels associated with cytosolic Ca signaling regulates the pathogenesis of PAH. Limited information is currently available on the role of Cl channels in PASMCs.

Mitofusin 2 positively regulates Ca signaling by tethering the sarcoplasmic reticulum and mitochondria in rat aortic smooth muscle cells.

Mitochondria buffer cytosolic Ca increases following Ca influx from extracellular spaces, and Ca release from intracellular Ca store sites under physiological circumstances. Therefore, close contact of mitochondria with the sarcoplasmic reticulum (SR) is required for maintaining Ca homeostasis. Mitofusin 2 (Mfn2) localizes in both mitochondrial and SR membranes and is hypothesized to optimize the distance and Ca transfer between these organelles.

Involvement of small-conductance Ca-activated K (SK2) channels in spontaneous Ca oscillations in rat pinealocytes.

Melatonin secretion from the pineal glands regulates circadian rhythms in mammals. Melatonin production is decreased by an increase in cytosolic Ca concentration following the activation of nicotinic acetylcholine receptors in parasympathetic systems. We previously reported that pineal Ca oscillations were regulated by voltage-dependent Ca channels and large-conductance Ca-activated K (BK) channels, which inhibited melatonin production.

Ca Signaling and Proliferation via Ca-Sensing Receptors in Human Hepatic Stellate LX-2 Cells.

Hepatic stellate cells (HSCs) play a significant role in the development of chronic liver diseases. Hepatic damage activates HSCs and results in hepatic fibrosis. The functions of activated HSCs require an increase in the cytosolic Ca concentration ([Ca]).

A molecular complex of Ca1.2/CaMKK2/CaMK1a in caveolae is responsible for vascular remodeling via excitation-transcription coupling.

Elevation of intracellular Ca2+ concentration ([Ca2+]i) activates Ca2+/calmodulin-dependent kinases (CaMK) and promotes gene transcription. This signaling pathway is referred to as excitation–transcription (E-T) coupling. Although vascular myocytes can exhibit E-T coupling, the molecular mechanisms and physiological/pathological roles are unknown.

Downregulation of Ca-Activated Cl Channel TMEM16A Mediated by Angiotensin II in Cirrhotic Portal Hypertensive Mice.

Portal hypertension is defined as an increased pressure in the portal venous system and occurs as a major complication in chronic liver diseases. The pathological mechanism underlying the pathogenesis and development of portal hypertension has been extensively investigated. Vascular tone of portal vein smooth muscles (PVSMs) is regulated by the activities of several ion channels, including Ca-activated Cl (Cl) channels.

SKF96365 activates calcium-sensing receptors in pulmonary arterial smooth muscle cells.

In pulmonary arterial smooth muscle cells (PASMCs), an increase in the cytosolic Ca concentration ([Ca]) is involved in many physiological processes such as cell contraction and proliferation. However, chronic [Ca] increases cause pulmonary vasoconstriction and vascular remodeling, resulting in pulmonary arterial hypertension (PAH). Therefore, [Ca] signaling plays a substantial role in the regulation of physiological and pathological functions in PASMCs.

Involvement of TREK1 channels in the proliferation of human hepatic stellate LX-2 cells.

Activation of hepatic stellate cells (HSCs) causes hepatic fibrosis and results in chronic liver diseases. Although activated HSC functions are facilitated by an increase in the cytosolic Ca concentration ([Ca]), the pathophysiological roles of ion channels are largely unknown. In the present study, functional analyses of the two-pore domain K (K) channels, which regulate the resting membrane potential and [Ca], were performed using the human HSC line, LX-2.

Comparative analysis of age in monocrotaline-induced pulmonary hypertensive rats.

Pulmonary arterial hypertension (PAH) is a rare, progressive, and fatal cardiovascular/lung disease. The incidence rate is affected by age. Monocrotaline (MCT, 60 mg/kg)-treated rats are widely used as an experimental PAH model.