In inflamed tissue, nociceptors show increased sensitivity to noxious heat, which may account for heat hyperalgesia. In unmyelinated nociceptive afferents in rat skin in vitro, a drop of heat threshold and an increase in heat responses were induced by experimental elevation of intracellular calcium ([Ca2+]i) levels with the calcium ionophore ionomycin (10 microM). Similar results were obtained ...

Myometrial smooth muscle contractility is regulated predominantly through the reversible phosphorylation of MYLs (myosin light chains), catalysed by MYLK (MYL kinase) and MYLP (MYL phosphatase) activities. MYLK is activated by Ca2+-calmodulin, and most uterotonic agonists operate through myometrial receptors that increase [Ca2+]i (intracellular Ca2+ concentration). Moreover, there is substantia...

Airway smooth muscle tone is ultimately generated by phosphorylation of myosin light chain, which is regulated by the balance between concentrations of Ca2+ and sensitivity to Ca2+ in the cytosolic side. The former is due to the Ca2+ influx passing through ion channels (Ca2+ dynamics), leading to activation of myosin light chain kinase, and the latter is due to Rho-kinase (Ca2+ sensitization), ...

In human cardiomyopathy, anatomical abnormalities such as hypertrophy and fibrosis contribute to the risk of ventricular arrhythmias and sudden death. Here we have shown that increased myofilament Ca2+ sensitivity, also a common feature in both inherited and acquired human cardiomyopathies, created arrhythmia susceptibility in mice, even in the absence of anatomical abnormalities. In mice expre...

The mechanism of Ca2+ sensitization of contraction has not been elucidated in airway smooth muscle (SM). To determine the role of a small G protein, rhoA p21, and its target protein, rho-associated coiled coil-forming protein kinase (ROCK), in receptor-coupled Ca2+ sensitization of airway SM, we studied the effect of (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexane carboxamide dihydrochl...

Increased sensitivity to intracellular Ca2+ concentration ([Ca2+]) is an important mechanism for agonist-induced contraction of airway smooth muscle, but the signal transduction pathways involved are uncertain. We studied Ca2+ sensitization with acetylcholine (ACh) and endothelin (ET)-1 in porcine tracheal smooth muscle by measuring contractions at a constant [Ca2+] in strips permeabilized with...

A cytosolic factor from sperm (SF) is thought to be responsible for the generation of intracellular calcium oscillations ([Ca2+]i) associated with fertilization in mammalian oocytes. Whether or not mouse oocytes injected with SF exhibit modifications of their Ca2+ release mechanisms similar to those observed in fertilized oocytes is not known and this was investigated here by injecting porcine ...

Airway hyperresponsiveness (AHR) and inflammation are key pathophysiological features of asthma. Enhanced contraction of bronchial smooth muscle (BSM) is one of the causes of the AHR. It is thus important for development of asthma therapy to understand the change in the contractile signaling of airway smooth muscle cells associated with the AHR. In addition to the Ca2+-mediated phosphorylation ...

The polyphenolic 1,2,3,4,6-penta-O-galloyl-beta-D-glucose from several medicinal herbs triggers apoptosis and has, thus, been proposed for treatment of malignancy. The substance is at least partially effective through caspase activation. In analogy to apoptosis of nucleated cells, erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and by phosphatidylser...

Robertson, Tom P., Philip I. Aaronson, and Jeremy P. T. Ward. Ca2 sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent. Am J Physiol Lung Cell Mol Physiol 284: L1121–L1126, 2003. First published February 28, 2003; 10.1152/ajplung.00422. 2002.—The main aim of this study was to determine the effects of endothelium removal on tension and intracellular Ca2 ([Ca...