Search results for "Calcium Channel"
showing 10 items of 204 documents
Stromal Interaction Molecule 1 (STIM1) Is Involved in the Regulation of Mitochondrial Shape and Bioenergetics and Plays a Role in Oxidative Stress
2012
Calcium ions are involved in a plethora of cellular functions including cell death and mitochondrial energy metabolism. Store-operated Ca(2+) entry over the plasma membrane is activated by depletion of intracellular Ca(2+) stores and is mediated by the sensor STIM1 and the channel ORAI1. We compared cell death susceptibility to oxidative stress in STIM1 knock-out and ORAI1 knockdown mouse embryonic fibroblasts and in knock-out cells with reconstituted wild type and dominant active STIM1. We show that STIM1 and ORAI1 deficiency renders cells more susceptible to oxidative stress, which can be rescued by STIM1 and ORAI1 overexpression. STIM1 knock-out mitochondria are tubular, have a higher Ca…
Molecular basis of early epithelial response to streptococcal exotoxin: role of STIM1 and Orai1 proteins
2011
Streptolysin O (SLO) is a cholesterol-dependent cytolysin (CDC) from Streptococcus pyogenes. SLO induces diverse types of Ca(2+) signalling in host cells which play a key role in membrane repair and cell fate determination. The mechanisms behind SLO-induced Ca(2+) signalling remain poorly understood. Here, we show that in NCI-H441 cells, wild-type SLO as well as non-pore-forming mutant induces long-lasting intracellular Ca(2+) oscillations via IP(3) -mediated depletion of intracellular stores and activation of store-operated Ca(2+) (SOC) entry. SLO-induced activation of SOC entry was confirmed by Ca(2+) add-back experiments, pharmacologically and by overexpression as well as silencing of ST…
Alteration of loosely bound calcium in the guinea pig organ of Corti after treatment with diltiazem as calcium channel blocker
1997
After oral administration of the organic calcium channel blocker diltiazem to guinea pigs for 7 days, calcium ions were precipitated with potassium antimonate in the cochleae. The spatial distribution of the precipitates was studied by energy-filtering transmission electron microscopy and the amount of the ultrastructural reaction products formed was determined semiquantitatively by an image processing system. Compared with untreated control ears, the number of the formed precipitates was reduced drastically in the inner hair cells after diltiazem treatment. In addition, electron microscopic analysis revealed that the number of calcium precipitates attached at the basolateral membrane of th…
Adrenoceptor-mediated effects on calcium channel currents are antagonized by 5?-(N-ethyl)-carboxamido-adenosine in guinea-pig atrial cells
1992
In guinea-pig atrial myocytes, the effects of the adenosine analogue 5′-(N-ethyl)-carboxamido-adenosine (NECA) in the presence of isoprenaline (ISO) on Ca2+ channel activity were analyzed. Single Ca2+ channel currents were recorded from cell-attached patches by application of several hundred 100 ms depolarizing steps. Under control conditions, burstlike activity of channel openings during some depolarizing steps were followed by variably long periods of quiescence (blank sweeps). During superfusion with ISO (100 nmol/l), ensemble-averaged (mean) current was increased by about 150%. The underlying mechanism was found to be a significant increase in the channel availability, defined as the ra…
Different mechanism of relaxation induced by aporphine alkaloids in rat uterus.
1993
Abstract We have examined the uterine relaxant action of three aporphine molecules (S-glaucine, S-boldine and R-apomorphine) in two experimental conditions, with and without calcium in the bathing solution, and compared these effects with those obtained with the calcium antagonists verapamil and diltiazem. The present study shows that the alkaloids relax the uterine muscle but with different mechanisms of action. In Ca2+-containing solution all three alkaloids relaxed the uterus previously contracted by KCl or acetylcholine, but in Ca2+-free medium only R-apomorphine was able to relax oxytocin-induced contraction. The calcium antagonists, verapamil and diltiazem, relaxed KCl- or acetylcholi…
Acute and Chronic Captopril, but Not Prazosin or Nifedipine, Normalize Alterations in Adrenergic Intracellular Ca2+ Handling Observed in the Mesenter…
2004
The effect of hypertension and acute (36-h) or chronic (from age 6 to 16 weeks) antihypertensive treatment with prazosin (2 mg kg(-1) per day), nifedipine (50 mg kg(-1) per day), or captopril (50 mg kg(-1) per day) on Ca2+ mobilization due to alpha1-adrenoceptor activation was analyzed in functional studies using arterial rings [four conductance/distributing vessels: aorta, main mesenteric, iliac, and tail arteries and two resistance vessels; first and second small mesenteric artery branches obtained from spontaneously hypertensive rats (SHR, 6 and 16 weeks old) and age-matched Wistar Kyoto rats (WKY)]. Maximal response to noradrenaline in the presence of extracellular Ca2+ is not affected …
Special Considerations for Antihypertensive Agents in Dialysis Patients
2010
Hypertension is present in most patients with end-stage renal disease and likely contributes to the premature cardiovascular disease in dialysis patients. Previous practice guidelines have recommended that, in patients on chronic dialysis, blood pressure (BP) should be reduced below 130/80 mm Hg. This is based on opinions but not strong evidence, since no concrete information exists about which BP values should be the parameter to follow and which should be the target BP values. The majority of the antihypertensive agents can be used in this population, but the pharmacokinetics altered by the impaired kidney function and dialyzability influence the appropriate dosage as well as the time and…
Efficacy of combination therapy with angiotensin-converting enzyme inhibitor and calcium channel blocker in hypertension.
2012
There are few clinical trials that provide evidence to support the hypothesis that combined therapies offer a favorable risk-benefit ratio in the reduction of cardiovascular mortality and morbidity. Combined therapies containing an angiotensin-converting enzyme inhibitor (ACEI) with a calcium channel blocker (CCB) is one of the recommended combinations in the reappraisal of the European Society of Hypertension.The authors have performed a systematic review of the available clinical evidence on the use of combined therapies containing an ACEI with a CCB versus other combinations in the management of arterial hypertension (HT) and in the reduction of cardiovascular morbidity/mortality, accord…
Relaxation by Calcium Antagonists of Potassium-contracted Trachea from Normal and Sensitized Guinea-pigs: Influence of Epithelium and the Surface of …
1993
Abstract A technique by which drug access was restricted to either the mucosal or the adventitial surface of tracheal rings, isolated from normal (unsensitized) or sensitized guinea-pigs, was used to study the role of the epithelium in the relaxation produced by calcium antagonists (verapamil, nifedipine, cinnarizine and flunarizine) of K+-induced contraction. In trachea from normal guinea-pigs, the relaxation to verapamil for unrestricted or mucosal drug entry was reduced in the absence of epithelium, whereas the relaxation produced by nifedipine, cinnarizine or flunarizine was unchanged. In sensitized trachea, the relaxation elicited by the calcium antagonists tested was similar in intact…
The Sources of Ca2+ for Muscarinic Receptor-induced Contraction in the Rat Ileum
1996
Abstract The contractile responses obtained by activation of different muscarinic receptor subtypes in the longitudinal muscle of the rat ileum and especially the responses of this muscle to acetylcholine in a Ca2+-free medium have been investigated. In Ca2+-containing solution, acetylcholine elicited similar concentration-dependent contractile responses in the duodenum, jejunum and ileum strips of the rat intestine. The response to a maximal concentration of the agonist (1 μM) consisted of a rapid phasic response followed by a slower tonic one. Nifedipine completely relaxes or inhibits the sustained response and only partially diminishes the phasic one, which suggests that the phasic contr…