Acute lung injury is a common complication after severe trauma, which predisposes patients to multiple organ failure. This syndrome largely accounts for the late mortality that arises and despite many theories, pathological mechanism not fully understood. Discovery of histone-induced toxicity in mice presents new dimension elucidating underlying pathophysiology.To investigate roles circulating histones trauma-induced injury.Circulating histone levels with trauma were determined correlated...

1. The perforated patch technique with nystatin or amphotericin was used to record whole cell currents activated by adenosine in smooth muscle cells isolated enzymatically from pig coronary arteries. 2. Adenosine (5‐40 microM) an outward current at a holding potential of 0 mV 5 mM [K+]o and inward ‐60 143 [K+]o. dependence the reversal for adenosine‐activated on suggests that it flows through K+ channels, while its current‐voltage relation is consistent channels showing little voltage...

C-reactive protein (CRP) is an acute-phase that plays important defensive role in innate immunity against bacterial infection, but it also upregulated many noninfectious diseases. The generic function of this highly conserved molecule diseases range from inflammation, trauma, and malignancy not well understood. In article, we demonstrate CRP defends the human body toxicity histones released into circulation after extensive cell death. vitro, significantly alleviates histone-induced...

Caveolins are coat proteins of caveolae, small flask-shaped pits the plasma membranes most cells. Aside from roles in caveolae formation, caveolins recruit, retain and regulate many caveolae-associated signalling molecules. Caveolin-protein interactions commonly considered to occur between a ∼20 amino acid region within caveolin, caveolin scaffolding domain (CSD), an aromatic-rich binding motif (CBM) on partner (фXфXXXXф, фXXXXфXXф or фXфXXXXфXXф, where ф is aromatic X unspecified acid). The...

1. Whole‐cell potassium currents were studied in single smooth muscle cells enzymatically isolated from pig coronary arteries. 2. In small diameter branches of the left anterior descending artery (LAD), an inward rectifier current (IK(IR)) was identified, which inhibited by extracellular barium ions, suggesting presence (KIR) channels. 3. The conductance for IK(IR) measured 6, 12, 60 and 140 mM a function membrane potential concentration. 4. On hyperpolarization, activated along exponential...

1. Intracellular pH (pHi) was recorded in isolated sheep cardiac Purkinje fibres using liquid sensor ion‐selective microelectrodes conjunction with conventional (3 M‐KCl) (to record membrane potential). 2. In HEPES‐buffered solution (pH0 7.4), pHi recovery from an intracellular acid load (20 mM‐NH4Cl removal) blocked by 1 mM‐amiloride, consistent the inhibition of Na(+)‐H+ exchange. Replacement HEPES buffer CO2‐HCO3‐ caused a transient acidosis followed amiloride‐resistant to more alkaline...

The stress-activated protein kinase p38 and nitric oxide (NO) are proposed downstream effectors of excitotoxic cell death. Although the postsynaptic density PSD95 can recruit calcium-dependent neuronal NO synthase (nNOS) to mouth calcium-permeable NMDA receptor, depletion inhibits excitotoxicity, possibility that selective uncoupling nNOS from might be neuroprotective is unexplored. relationship between stress–generated activation p38, significance PSD95–nNOS interaction also remain unclear....

Abstract Many cell types have significant negative resting membrane potentials (RMPs) resulting from the activity of potassium‐selective and chloride‐selective ion channels. In excitable cells, such as neurones, rapid changes in permeability underlie generation action potentials. Chondrocytes less RMPs role RMP is not clear. Here we examine basis chondrocyte possible physiological benefits. We demonstrate that maintenance involves gadolinium‐sensitive cation Pharmacological inhibition these...

The paraventricular nucleus (PVN) of the hypothalamus has been described as "autonomic master controller". It co-ordinates critical physiological responses through control hypothalamic-pituitary-adrenal (HPA)-axis, and by modulation sympathetic parasympathetic branches central nervous system. PVN comprises several anatomical subdivisions, including parvocellular/ mediocellular subdivision, which contains neurones projecting to medulla spinal cord. Consensus indicates that output from...

1. The perforated patch technique with amphotericin B was used to record whole‐cell currents activated by hypoxia in smooth muscle cells, isolated enzymatically from pig coronary arteries. 2. Superfusion hypoxic solution (O2 partial pressure, 25‐40 mmHg) an inward current at ‐60 mV 143 mM extracellular K+. reversal potential of the induced shifted [K+] as expected for a K+ current, while its current‐voltage relation consistent channels showing little voltage dependence. 3. hypoxia‐induced...

Arterial ATP-sensitive K + (K ATP ) channels are critical regulators of vascular tone, forming a focal point for signaling by many vasoactive transmitters that alter smooth muscle contractility and so blood flow. Clinically, these form the target antianginal antihypertensive drugs, their genetic disruption leads to hypertension sudden cardiac death through coronary vasospasm. However, whereas biochemical basis channel modulation is well-studied, little known about structural or spatial...

Abstract Aim Long QT syndrome (LQTS) and catecholaminergic polymorphism ventricular tachycardia (CPVT) are inherited cardiac disorders often caused by mutations in ion channels. These arrhythmia syndromes have recently been associated with calmodulin (CaM) variants. Here, we investigate the impact of arrhythmogenic variants D131E Q135P on CaM's structure–function relationship. Our study focuses L‐type calcium channel Ca v 1.2, a crucial component action potential excitation–contraction...

The role of filamins in actin cross-linking and membrane stabilization is well established, but recently their ability to interact with a variety transmembrane receptors signaling proteins has led speculation additional roles scaffolding signal transduction. Here we report direct interaction between filamin-A Kir2.1, an isoform inwardly rectifying potassium channel expressed vascular smooth muscle important regulator tone. Yeast two-hybrid screening porcine coronary artery cDNA library using...

Objective The vasoconstrictor angiotensin II (Ang II) acts at Gq/11-coupled receptors to suppress ATP-sensitive potassium (KATP) channel activity via activation of protein kinase C (PKC). aim this study was determine the PKC isoforms involved in Ang II-induced inhibition aortic KATP and investigate potential mechanisms by which these specifically target ion channels.

Exchange proteins directly activated by cyclic AMP (Epacs or cAMP-GEF) represent a family of novel cAMP-binding effector proteins. The identification Epacs and the recent development pharmacological tools that discriminate between cAMP-mediated pathways have revealed previously unrecognized roles for cAMP are independent its traditional target cAMP-dependent protein kinase (PKA). Here we show Epac exists in complex with vascular ATP-sensitive potassium (KATP) channel subunits activation...

Transient receptor potential vanilloid type 4 (TRPV4) and calcium-activated potassium channels (KCa ) mediate osmosensing in many tissues. Both TRPV4 KCa are found the paraventricular nucleus (PVN) of hypothalamus, an area critical for sympathetic control cardiovascular renal function. Here, we have investigated whether functionally couple to PVN parvocellular neurones characterized, pharmacologically, subtype channel involved.

Key points Relaxation of vascular smooth muscle, which increases blood vessel diameter, is often mediated through vasodilator‐induced elevations intracellular 3′‐5′‐cyclic adenosine monophosphate (cAMP), although the mechanisms are incompletely understood. In this study we investigate role novel cAMP effector e xchange p rotein directly a ctivated by c AMP (Epac) in mediating vasorelaxation rat mesenteric arteries. We show that Epac mediates arteries facilitating opening several subtypes Ca...

Abstract Single-molecule research techniques such as patch-clamp electrophysiology deliver unique biological insight by capturing the movement of individual proteins in real time, unobscured whole-cell ensemble averaging. The critical first step analysis is event detection, so called “idealisation”, where noisy raw data are turned into discrete records protein movement. To date there have been practical limitations idealisation; high quality idealisation typically laborious and becomes...

Bioenergetics of artery smooth muscle cells is critical in cardiovascular health and disease. An acute rise metabolic demand causes vasodilation systemic circulation while a chronic shift bioenergetic profile may lead to vascular diseases. A decrease intracellular ATP level trigger physiological responses dedifferentiation contractile proliferative migratory phenotype often observed during pathological processes. Although it now possible dissect multiple building blocks components...