Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis and meningitis. Life-threatening acute cardiac complications are common in pneumococcal infection compared to bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered sustained by circulating pneumolysin (PLY). Using mouse model...

Chondrocytes are the resident cells of articular cartilage and responsible for synthesising a range collagenous non-collagenous extracellular matrix macromolecules. Whilst chondrocytes exist at low densities in tissue (1-10% total volume mature cartilage) they extremely active capable responding to mechanical biochemical stimuli. These responses necessary maintenance viable may be compromised inflammatory diseases such as arthritis. Although non-excitable their plasma membrane contains rich...

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...

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.

Abstract Chondrocytes possess the capacity to transduce load‐induced mechanical stimuli into electrochemical signals. The aim of this study was functionally characterize an ion channel activated in response membrane stretch isolated primary equine chondrocytes. We used patch‐clamp electrophysiology and immunohistochemistry examine its distribution articular cartilage. In cell‐attached patch experiments, application negative pressures pipette (in range 20–200 mmHg) currents six seven patches....

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...

Abstract Chondrogenesis is a multistep process, in which cartilage progenitor cells generate tissue with distinct structural and functional properties. Although several approaches to regeneration rely on the differentiation of implanted cells, temporal transcriptomic landscape vitro chondrogenesis different models has not been reported. Using RNA sequencing, we examined differences gene expression patterns during formation micromass cultures embryonic limb bud-derived progenitors. Principal...

Ion channels play important roles in chondrocyte mechanotransduction. The transient receptor potential vanilloid (TRPV) subfamily of ion consists six members. TRPV1-4 are temperature sensitive calcium-permeable, relatively non-selective cation whereas TRPV5 and TRPV6 show high selectivity for calcium over other cations. In this study we investigated the effect time culture passage number on expression TRPV4, articular chondrocytes isolated from equine metacarpophalangeal joints. Polyclonal...

ATP-sensitive potassium channels (K(ATP) channels) of arterial smooth muscle are important regulators tone, and hence blood flow, in response to vasoactive transmitters. Recent biochemical electron microscopic evidence suggests that these localise small vesicular invaginations the plasma membrane, known as caveolae, interact with caveolae-associated protein, caveolin. Here we report interaction caveolin functionally regulates activity vascular subtype K(ATP) channel, Kir6.1/SUR2B....

Background and Purpose Chondrocytes exist within cartilage serve to maintain the extracellular matrix. It has been postulated that osteoarthritic ( OA ) chondrocytes lose ability regulate their volume, affecting matrix production. In previous studies, we identified expression of epithelial sodium channels ENaC in human chondrocytes, but function remained unknown. Although typically N a + transport roles, it is also involved cell volume regulation rat hepatocytes. member degenerin D eg)...

Chondrocytes are the uniquely resident cells found in all types of cartilage and key to their function is ability respond mechanical loads with changes metabolic activity. This mechanotransduction property is, part, mediated through activity a range expressed transmembrane channels; ion channels, gap junction proteins, porins. Appropriate expression channels has been shown essential for production extracellular matrix differential correlated musculoskeletal diseases such as osteoarthritis...

ObjectiveThe anterior cruciate ligament transection (ACLT) rabbit osteoarthritis (OA) model confers permanent knee instability and induces joint degeneration. The degeneration process is complex, but includes chondrocyte apoptosis OA-like loss of cartilage integrity. Previously, we reported that activation a volume-sensitive Cl− current (ICl,vol) can mediate cell shrinkage in articular chondrocytes. Our objective was therefore to investigate whether ICl,vol activated the early stages ACLT OA...