共查询到20条相似文献,搜索用时 0 毫秒
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Laura Vay Esther Hernández-SanMiguel Jaime Santo-Domingo Carmen D. Lobatón Alfredo Moreno Mayte Montero Javier Alvarez 《The Journal of physiology》2007,580(1):39-49
The recent availability of activators of the mitochondrial Ca2+ uniporter allows direct testing of the influence of mitochondrial Ca2+ uptake on the overall Ca2+ homeostasis of the cell. We show here that activation of mitochondrial Ca2+ uptake by 4,4',4"-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) or kaempferol stimulates histamine-induced Ca2+ release from the endoplasmic reticulum (ER) and that this effect is enhanced if the mitochondrial Na+ –Ca2+ exchanger is simultaneously inhibited with CGP37157. This suggests that both Ca2+ uptake and release from mitochondria control the ability of local Ca2+ microdomains to produce feedback inhibition of inositol 1,4,5-trisphosphate receptors (InsP3 Rs). In addition, the ability of mitochondria to control Ca2+ release from the ER allows them to modulate cytosolic Ca2+ oscillations. In histamine stimulated HeLa cells and human fibroblasts, both PPT and kaempferol initially stimulated and later inhibited oscillations, although kaempferol usually induced a more prolonged period of stimulation. Both compounds were also able to induce the generation of Ca2+ oscillations in previously silent fibroblasts. Our data suggest that cytosolic Ca2+ oscillations are exquisitely sensitive to the rates of mitochondrial Ca2+ uptake and release, which precisely control the size of the local Ca2+ microdomains around InsP3 Rs and thus the ability to produce feedback activation or inhibition of Ca2+ release. 相似文献
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Mei Hong Zhu Tae Wan Kim Seungil Ro Wei Yan Sean M. Ward Sang Don Koh Kenton M. Sanders 《The Journal of physiology》2009,587(20):4905-4918
Interstitial cells of Cajal (ICC) are unique cells that generate electrical pacemaker activity in gastrointestinal (GI) muscles. Many previous studies have attempted to characterize the conductances responsible for pacemaker current and slow waves in the GI tract, but the precise mechanism of electrical rhythmicity is still debated. We used a new transgenic mouse with a bright green fluorescent protein (copGFP) constitutively expressed in ICC to facilitate study of these cells in mixed cell dispersions. We found that ICC express a specialized 'slow wave' current. Reversal of tail current analysis showed this current was due to a Cl− selective conductance. ICC express ANO1, a Ca2+ -activated Cl− channel. Slow wave currents are not voltage dependent, but a secondary voltage-dependent process underlies activation of these currents. Removal of extracellular Ca2+ , replacement of Ca2+ with Ba2+ , or extracellular Ni2+ (30 μ m ) blocked the slow wave current. Single Ca2+ -activated Cl− channels with a unitary conductance of 7.8 pS were resolved in excised patches of ICC. These are similar in conductance to ANO1 channels (8 pS) expressed in HEK293 cells. Slow wave current was blocked in a concentration-dependent manner by niflumic acid (IC50 = 4.8 μ m ). Slow wave currents are associated with transient depolarizations of ICC in current clamp, and these events were blocked by niflumic acid. These findings demonstrate a role for a Ca2+ -activated Cl− conductance in slow wave current in ICC and are consistent with the idea that ANO1 participates in pacemaker activity. 相似文献
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A. Mark Evans 《The Journal of physiology》2006,574(1):113-123
All cells respond to metabolic stress. However, a variety of specialized cells, commonly referred to as O2 -sensing cells, are acutely sensitive to relatively small changes in P O2 . Within a variety of organisms such O2 -sensing cells have evolved as vital homeostatic mechanisms that monitor O2 supply and alter respiratory and circulatory function, as well as the capacity of the blood to transport O2 . Thereby, arterial P O2 may be maintained within physiological limits. In mammals, for example, two key tissues that contribute to this process are the pulmonary arteries and the carotid bodies. Constriction of pulmonary arteries by hypoxia optimizes ventilation–perfusion matching in the lung, whilst carotid body excitation by hypoxia initiates corrective changes in breathing patterns via increased sensory afferent discharge to the brain stem. Despite extensive investigation, the precise mechanism(s) by which hypoxia mediates these responses has remained elusive. It is clear, however, that hypoxia inhibits mitochondrial function in O2 -sensing cells over a range of P O2 that has no such effect on other cell types. This raised the possibility that AMP-activated protein kinase might function to couple mitochondrial oxidative phosphorylation to Ca2+ signalling mechanisms in O2 -sensing cells and thereby underpin pulmonary artery constriction and carotid body excitation by hypoxia. Our recent investigations have provided significant evidence in support of this view. 相似文献
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The recently discovered apical calcium channels CaT1 (TRPV6) and ECaC (TRPV5) belong to a family of six members called the 'TRPV family'. Unlike the other four members which are nonselective cation channels functioning as heat or osmolarity sensors in the body, CaT1 and ECaC are remarkably calcium-selective channels which serve as apical calcium entry mechanisms in absorptive and secretory tissues. CaT1 is highly expressed in the proximal intestine, placenta and exocrine tissues, whereas ECaC expression is most prominent in the distal convoluted and connecting tubules of the kidney. CaT1 in the intestine is highly responsive to 1,25-dihydroxyvitamin D3 and shows both fast and slow calcium-dependent feedback inhibition to prevent calcium overload. In contrast, ECaC only shows slow inactivation kinetics and appears to be mostly regulated by the calcium load in the kidney. Outside the calcium-transporting epithelia, CaT1 is highly expressed in exocrine tissues such as pancreas, prostate and salivary gland. In these tissues it probably mediates re-uptake of calcium following its release by secretory vesicles. CaT1 also contributes to store-operated calcium entry in Jurkat T-lymphocytes and prostate cancer LNCaP cells, possibly in conjunction with other cellular components which link CaT1 activity to the filling state of the calcium stores. Finally, CaT1 expression is upregulated in prostate cancer and other cancers of epithelial origin, highlighting its potential as a target for cancer therapy. 相似文献
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