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Measurements of simultaneous force and intracellular Ca2+ concentration ([Ca2+]i) in rat uterine smooth muscle have been made to elucidate the mechanisms involved when force produced spontaneously, by high-K+ depolarization or carbachol is altered by a change of intracellular pH (pHi). Rises in force and [Ca2+]i were closely correlated for all forms of(More)
The regulation of contractile activity in smooth muscle cells involves rapid discrimination and processing of a multitude of simultaneous signals impinging on the membrane before an integrated functional response can be generated. The sarcolemma of smooth muscle cells is segregated into caveolar regions-largely identical with cholesterol-rich membrane(More)
Little is known about how hypercholesterolaemia affects Ca(2+) signalling in the vasculature of ApoE(-/-) mice, a model of atherosclerosis. Our objectives were therefore to determine (i) if hypercholesterolaemia alters Ca(2+) signalling in aortic endothelial cells before overt atherosclerotic lesions occur, (ii) how Ca(2+) signals are affected in older(More)
Apolipoprotein-E knockout (ApoE(-/-)) mice develop hypercholesterolemia and are a useful model of atherosclerosis. Hypercholesterolemia alters intracellular Ca(2+) signalling in vascular endothelial cells but our understanding of these changes, especially in the early stages of the disease process, is limited. We therefore determined whether(More)
To investigate the role of myosin light chain kinase (MLCK) in phasic contractions of intact smooth muscle, we have applied Wortmannin, an MLCK inhibitor, to strips of guinea-pig ureter. Simultaneous measurements of electrical activity, intracellular [Ca2+] ([Ca2+]i) and phasic force showed that Wortmannin (1-4 microM) abolishes force with little or no(More)
1. We have altered intracellular (pHi) and extracellular pH (pHo) in the smooth muscle of guinea-pig ureter and determined the effects on evoked phasic contractions. In order to investigate the mechanisms underlying the effects of pH alteration, intracellular Ca2+ ([Ca2+]i), pHi, electrical activity and force were measured. 2. Intracellular acidification,(More)
1. We investigated the relationship between the action potential, Ca2+ and phasic force in intact guinea-pig ureter, following physiological activation. 2. The action potential elicited a Ca2+ transient consisting of three components: a fast increment, associated with the first action potential spike, a slower increment, associated with subsequent spikes(More)
Although there is evidence that caveolae and cholesterol play an important role in myocyte signalling processes, details of the mechanisms involved remain sparse. In this paper we have studied for the first time the clinically relevant intact coronary artery and measured in situ Ca(2+) signals in individual myocytes using confocal microscopy. We have(More)
1. We have investigated the effect of cyclopiazonic acid (CPA), an inhibitor of the sarcoplasmic reticulum (SR) Ca2+-ATPase on excitation-contraction (EC) coupling in guinea-pig ureter, by measuring membrane currents, action potentials, intracellular [Ca2+] and force. 2. CPA (20 micrometers) significantly enhanced the amplitude and duration of phasic(More)
Calcium signalling in smooth muscles is complex, but our understanding of it has increased markedly in recent years. Thus, progress has been made in relating global Ca2+ signals to changes in force in smooth muscles and understanding the biochemical and molecular mechanisms involved in Ca2+ sensitization, i.e. altering the relation between Ca2+ and force.(More)