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The sarcoplasmic reticulum (SR) in ventricular myocytes contains releasable Ca2+ for activating cellular contraction. Recent measurements of intra-SR (luminal) Ca2+ suggest a high diffusive Ca2+-mobility constant (DCaSR). This could help spatially to unify SR Ca2+-content ([Ca2+]SRT) and standardize Ca2+-release throughout the cell. But measurements of localized depletions of luminal Ca2+ (Ca2+-blinks), associated with local Ca2+-release (Ca2+-sparks), suggest DCaSR may actually be low. Here we describe a novel method for measuring DCaSR. Using a cytoplasmic Ca2+-fluorophore, we estimate regional [Ca2+]SRT from localized, caffeine-induced SR Ca2+-release. Caffeine microperfusion of one end of a guinea pig or rat myocyte diffusively empties the whole SR at a rate indicating DCaSR is 8-9 μm2/s, up to tenfold lower than previous estimates. Ignoring background SR Ca2+-leakage in our measurement protocol produces an artifactually high DCaSR (>40 μm2/s), which may also explain the previous high values. Diffusion-reaction modeling suggests that a low DCaSR would be sufficient to support local SR Ca2+-signaling within sarcomeres during excitation-contraction coupling. Low DCaSR also implies that [Ca2+]SRT may readily become spatially nonuniform, particularly under pathological conditions of spatially nonuniform Ca2+-release. Local control of luminal Ca2+, imposed by low DCaSR, may complement the well-established local control of SR Ca2+-release by Ca2+-channel/ryanodine receptor couplons. 相似文献
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65.
Pawel Piotr Liberski 《Molecular neurobiology》1994,8(1):67-77
Alzheimer’s disease, a prototypic nontransmissible cerebral amyloidosis, has no adequate experimental model. Several pathogenetic events, however, may be modeled and accurately studied in the transmissible cerebral amyloidoses of kuru, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and scrapie. The common neuropathological denominator in both types of cerebral amyloidoses is the presence of stellate kuru plaques, senile plaques, and pure neuritic plaques. These amyloid plaques consist of amyloid fibers, dystrophic neurites, and reactive astrocytes in different proportions. Microglial cells, which are regarded as amyloid producer/processor cells in Alzheimer’s disease, may play the same function in the transmissible cerebral amyloidoses. In both transmissible and nontransmissible amyloidoses, the impairment of axonal transport leads to accumulation of abnormally phosphorylated cytoskeleton proteins (such as neurofilament proteins and microtubule-associated protein τ), which eventually produce dystophic neurites observed as parts of plaque or as isolated pathological structures. 相似文献
66.
Michał Bijok Ewelina Gruszczynska Adam Kowalczyk Katarzyna Sikorska Agnieszka Walewska Pawel F. Kukolowicz 《Reports of Practical Oncology and Radiotherapy》2018,23(5):341-345
Aim
The aim of the study was to analyze the long-term stability of electron beams generated by the Novac11? IORT accelerator.Background
Novac11? (NRT®) is a mobile electron accelerator designed to irradiate small areas of tissue, up to 10?cm in diameter, with electron beams during surgical procedures. It is characterized by a great mobility guaranteed by a number of degrees of freedom enabling irradiation in the conditions of an operating theatre.Materials and methods
Over the period of January 2013 and September 2016, the measurement sessions of the output of clinically used beam qualities (6, 8 and 10?MeV) were carried out 41 times. Because of the unsatisfactory long-term stability, an extra procedure of tuning of the magnetron, suggested by the manufacturer, was introduced in October 2015, 15 measurements were performed since then. The output of the Novac11? accelerator was measured in the reference conditions recommended by the IAEA Report 398, the measurements of the charge in the ionization chamber at the reference depth were carried out with a Dose1? electrometer and a plane-parallel chamber PPC05? from IBA®.Results
The introduction of the tuning of the magnetron procedure resulted in satisfactory long-term stability of the measured outputs below 2%.Conclusions
After the introduction of the STV parameter tuning procedure, the long-term stability of the Novac11? output increased considerably and is within the values declared by the manufacturer. 相似文献67.
The prion protein is a membrane attached glycoprotein that is involved in binding of divalent copper ions. In vivo human and chicken PrPs exhibit SOD-like activity associated with octarepeat and hexarepeat regions, respectively, when bind Cu(II) ions. However, the species of Cu(II)-PrP involved in the Cu(II) center which determines the highest SOD-like activity is still unknown. The data presented here clearly show that the single Cu(II) ion bound to PrP octapeptide repeat region of mammalian prion and hexapeptide repeat region of avian prion via 4 His side-chain imidazoles reveals the highest SOD activity. 相似文献
68.
pH-Dependence of extrinsic and intrinsic H(+)-ion mobility in the rat ventricular myocyte, investigated using flash photolysis of a caged-H(+) compound 下载免费PDF全文
Passive H(+)-ion mobility within eukaryotic cells is low, due to H(+)-ion binding to cytoplasmic buffers. A localized intracellular acidosis can therefore persist for seconds or even minutes. Because H(+)-ions modulate so many biological processes, spatial intracellular pH (pH(i))-regulation becomes important for coordinating cellular activity. We have investigated spatial pH(i)-regulation in single and paired ventricular myocytes from rat heart by inducing a localized intracellular acid-load, while confocally imaging pH(i) using the pH-fluorophore, carboxy-SNARF-1. We present a novel method for localizing the acid-load. This involves the intracellular photolytic uncaging of H(+)-ions from a membrane-permeant acid-donor, 2-nitrobenzaldehyde. The subsequent spatial pH(i)-changes are consistent with intracellular H(+)-mobility and cell-to-cell H(+)-permeability constants measured using more conventional acid-loading techniques. We use the method to investigate the effect of reducing pH(i) on intrinsic (non-CO(2)/HCO(3)(-) buffer-dependent) and extrinsic (CO(2)/HCO(3)(-) buffer-dependent) components of H(i)(+)-mobility. We find that although both components mediate spatial regulation of pH within the cell, their ability to do so declines sharply at low pH(i). Thus acidosis severely slows intracellular H(+)-ion movement. This can result in spatial pH(i) nonuniformity, particularly during the stimulation of sarcolemmal Na(+)-H(+) exchange. Intracellular acidosis thus presents a window of vulnerability in the spatial coordination of cellular function. 相似文献
69.
The 3' part of the glucosamine-6-phosphate synthase gene from Histoplasma capsulatum was PCR amplified using degenerate primers
designed from the known glucosamine-6-phosphate synthase gene sequences, cloned and sequenced. The computer analysis of the
676 bp sequence revealed the presence of two introns. The identities of the deduced amino acid sequence to the corresponding
Saccharomyces cerevisiae and Candida albicans fragment are 65 and 63.8%, respectively.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
70.
Yunjiao Wang Pawel Paszek Caroline A Horton Douglas B Kell Michael RH White David S Broomhead Mark R Muldoon 《BMC systems biology》2011,5(1):23