Vision of the body, even when non-informative about stimulation, affects somatosensory processing. We investigated whether seeing the body also modulates autonomic control in the periphery by measuring skin temperature while manipulating vision. Using a mirror box, the skin temperature was measured from left hand dorsum while participants: (i) had the illusion of seeing their left hand, (ii) had the illusion of seeing an object at the same location or (iii) looked directly at their contralateral right hand. Skin temperature of the left hand increased when participants had the illusion of directly seeing that hand but not in the other two view conditions. In experiment 2, participants viewed directly their left or right hand, or the box while we recorded both hand dorsum temperatures. Temperature increased in the viewed hand but not the contralateral hand. These results show that seeing the body produces limb-specific modulation of thermal regulation. 相似文献
The roles of intracellular calcium in the regulation of cell metabolism and cell membrane permeability are highlighted with examples taken from recent studies. 相似文献
Dendritic spines arise as small protrusions from the dendritic shaft of various types of neuron and receive inputs from excitatory axons. Ever since dendritic spines were first described in the nineteenth century, questions about their function have spawned many hypotheses. In this review, we introduce understanding of the structural and biochemical properties of dendritic spines with emphasis on components studied with imaging methods. We then explore advances in in vivo imaging methods that are allowing spine activity to be studied in living tissue, from super-resolution techniques to calcium imaging. Finally, we review studies on spine structure and function in vivo. These new results shed light on the development, integration properties and plasticity of spines. 相似文献
An understanding of deformation of cardiovascular tissue under hemodynamic load is crucial for understanding the health and disease of blood vessels. In the present work, an epi‐detected stimulated Raman scattering (epi‐SRS) imaging platform was designed for in situ functional imaging of vascular smooth muscle cells (VMSCs) in fresh coronary arteries. For the first time, the pressure‐induced morphological deformation of fresh VSMCs was imaged with no fixation and in a label‐free manner. The relation between the loading pressure and the morphological parameters, including angle and length of the VSMCs, were apparent. The morphological responses of VMSCs to drug treatment were also explored, to demonstrate the capability of functional imaging for VSMCs by this method. The time‐course imaging revealed the drug induced change in angle and length of VSMCs. The present study provides a better understanding of the biomechanical framework of blood vessels, as well as their responses to external stimulations, which are fundamental for developing new strategies for cardiovascular disease treatment. 相似文献
Peripheral arterial disease (PAD) can further cause lower limb ischemia. Quantitative evaluation of the vascular perfusion in the ischemic limb contributes to diagnosis of PAD and preclinical development of new drug. In vivo time‐series indocyanine green (ICG) fluorescence imaging can noninvasively monitor blood flow and has a deep tissue penetration. The perfusion rate estimated from the time‐series ICG images is not enough for the evaluation of hindlimb ischemia. The information relevant to the vascular density is also important, because angiogenesis is an essential mechanism for post‐ischemic recovery. In this paper, a multiparametric evaluation method is proposed for simultaneous estimation of multiple vascular perfusion parameters, including not only the perfusion rate but also the vascular perfusion density and the time‐varying ICG concentration in veins. The target method is based on a mathematical model of ICG pharmacokinetics in the mouse hindlimb. The regression analysis performed on the time‐series ICG images obtained from a dynamic reflectance fluorescence imaging system. The results demonstrate that the estimated multiple parameters are effective to quantitatively evaluate the vascular perfusion and distinguish hypo‐perfused tissues from well‐perfused tissues in the mouse hindlimb. The proposed multiparametric evaluation method could be useful for PAD diagnosis.
The estimated perfusion rate and vascular perfusion density maps (left) and the time‐varying ICG concentration in veins of the ankle region (right) of the normal and ischemic hindlimbs. 相似文献
This study examined whether 60 Hz magnetic field (MF) exposure alters intracellular calcium levels ([Ca(2+)](i)) in isolated bovine adrenal chromaffin cells, a classic model of neural responses. [Ca(2+)](i) was monitored by fluorescence video imaging of cells loaded with the calcium indicator fluo-4 during exposures to magnetic flux densities of 0.01, 0.1, 1.0, 1.4, or 2.0 mT. MFs generated by Helmholtz coils constructed from bifilar wire allowed both 60 Hz field and sham exposures. Following a 5 min monitoring period to establish baseline patterns, cells were subjected for 10 min to a 60 Hz MF, sham field or no field. Reference calcium responses and assessment of cell excitability were obtained by the sequential addition of the nicotinic cholinergic receptor agonist dimethylphenylpiperazinium (DMPP) and a depolarizing concentration of KCl. Throughout an 8 day culture period, cells exhibited spontaneous fluctuations in [Ca(2+)](i). Comparisons of the number of cells exhibiting transients, the number and types of calcium transients, as well as the time during monitoring when transients occurred showed no significant differences between MF exposed cells and either sham exposed or nonexposed cells. With respect to the percentage of cells responding to DMPP, differences between 1 and 2 mT exposed cells and both nonexposed and sham exposed cells reached statistical significance during the first day in culture. No statistically significant differences were observed for responses to KCl. In summary, our data indicate that [Ca(2+)](i) in chromaffin cells is unaffected by the specific 60 Hz MF intensities used in this study. On the other hand, plasma membrane nicotinic receptors may be affected in a manner that is important for ligand-receptor interactions. 相似文献
Caveolae position CaV3.2 (T‐type Ca2+ channel encoded by the α‐3.2 subunit) sufficiently close to RyR (ryanodine receptors) for extracellular Ca2+ influx to trigger Ca2+ sparks and large‐conductance Ca2+‐activated K+ channel feedback in vascular smooth muscle. We hypothesize that this mechanism of Ca2+ spark generation is affected by age. Using smooth muscle cells (VSMCs) from mouse mesenteric arteries, we found that both Cav3.2 channel inhibition by Ni2+ (50 µM) and caveolae disruption by methyl‐ß‐cyclodextrin or genetic abolition of Eps15 homology domain‐containing protein (EHD2) inhibited Ca2+ sparks in cells from young (4 months) but not old (12 months) mice. In accordance, expression of Cav3.2 channel was higher in mesenteric arteries from young than old mice. Similar effects were observed for caveolae density. Using SMAKO Cav1.2?/? mice, caffeine (RyR activator) and thapsigargin (Ca2+ transport ATPase inhibitor), we found that sufficient SR Ca2+ load is a prerequisite for the CaV3.2‐RyR axis to generate Ca2+ sparks. We identified a fraction of Ca2+ sparks in aged VSMCs, which is sensitive to the TRP channel blocker Gd3+ (100 µM), but insensitive to CaV1.2 and CaV3.2 channel blockade. Our data demonstrate that the VSMC CaV3.2‐RyR axis is down‐regulated by aging. This defective CaV3.2‐RyR coupling is counterbalanced by a Gd3+ sensitive Ca2+ pathway providing compensatory Ca2+ influx for triggering Ca2+ sparks in aged VSMCs. 相似文献
Dynamic intravital imaging is essential for revealing ongoing biological phenomena within living organisms and is influenced primarily by several factors: motion artifacts, optical properties and spatial resolution. Conventional imaging quality within a volume, however, is degraded by involuntary movements and trades off between the imaged volume, imaging speed and quality. To balance such trade‐offs incurred by two‐photon excitation microscopy during intravital imaging, we developed a unique combination of interlaced scanning and a simple image restoration algorithm based on biological signal sparsity and a graph Laplacian matrix. This method increases the scanning speed by a factor of four for a field size of 212 μm × 106 μm × 130 μm, and significantly improves the quality of four‐dimensional dynamic volumetric data by preventing irregular artifacts due to the movement observed with conventional methods. Our data suggest this method is robust enough to be applied to multiple types of soft tissue. 相似文献
Oblique plane microscopy (OPM) is a form of light sheet microscopy that uses a single high numerical aperture microscope objective for both fluorescence excitation and collection. In this paper, measurements of the relative collection efficiency of OPM are presented. An OPM system incorporating two sCMOS cameras is then introduced that enables single isolated cardiac myocytes to be studied continuously for 22 seconds in two dimensions at 667 frames per second with 960 × 200 pixels and for 30 seconds with 960 × 200 × 20 voxels at 25 volumes per second. In both cases OPM is able to record in two spectral channels, enabling intracellular calcium to be studied via the probe Fluo‐4 AM simultaneously with the sarcolemma and transverse tubule network via the membrane dye Cellmask Orange. The OPM system was then applied to determine the spatial origin of spontaneous calcium waves for the first time and to measure the cell transverse tubule structure at their point of origin. Further results are presented to demonstrate that the OPM system can also be used to study calcium spark parameters depending on their relationship to the transverse tubule structure.
Interactions between voltage-gated calcium channels (Ca(V)s) and calmodulin (CaM) modulate Ca(V) function. In this study, we report the structure of a Ca(2+)/CaM Ca(V)1.2 C-terminal tail complex that contains two PreIQ helices bridged by two Ca(2+)/CaMs and two Ca(2+)/CaM-IQ domain complexes. Sedimentation equilibrium experiments establish that the complex has a 2:1 Ca(2+)/CaM:C-terminal tail stoichiometry and does not form higher order assemblies. Moreover, subunit-counting experiments demonstrate that in live cell membranes Ca(V)1.2s are monomers. Thus, contrary to previous proposals, the crystallographic dimer lacks physiological relevance. Isothermal titration calorimetry and biochemical experiments show that the two Ca(2+)/CaMs in the complex have different properties. Ca(2+)/CaM bound to the PreIQ C-region is labile, whereas Ca(2+)/CaM bound to the IQ domain is not. Furthermore, neither of lobes of apo-CaM interacts strongly with the PreIQ domain. Electrophysiological studies indicate that the PreIQ C-region has a role in calcium-dependent facilitation. Together, the data show that two Ca(2+)/CaMs can bind the Ca(V)1.2 tail simultaneously and indicate a functional role for Ca(2+)/CaM at the C-region site. 相似文献
Gamma-aminobutyric acid (GABA) is as an excitatory neurotransmitter during brain development. Activation of GABA(A) receptors in neonatal rat hippocampus results in chloride efflux and membrane depolarization sufficient to open voltage sensitive calcium channels. As development progresses, there is a decline in the magnitude of calcium influx subsequent to GABA(A) receptor activation and the number of cells that respond to GABA with excitation. By the second postnatal week in the rat, GABA action in the hippocampus is predominantly inhibitory. The functional consequences and endogenous regulation of developmental GABA-mediated excitation remains under-explored. Hippocampal neurons in the newborn male and female rat respond to GABA(A) receptor activation with increased intracellular calcium and are susceptible to GABA-mediated damage -- both being indicative of the excitatory nature of GABA. In the present study we observed that by postnatal day 7, only males are susceptible to GABA(A) agonist-induced damage and respond to GABA(A) agonist administration with elevated levels of intracellular calcium in cultured hippocampal neurons. By postnatal day 14, GABA(A) agonist administration was without effect on intracellular calcium in both males and females. The age-related sex difference in the impact of GABA(A) receptor activation correlates with a sex difference in chloride co-transporter expression. Males have elevated protein levels of pNKCC1 on PN0 and PN7, with no sex difference by PN14. In contrast, females displayed elevated levels of KCC2 on PN7. This converging evidence infers that sex affects the duration of GABA(A) receptor-mediated excitation during normal hippocampal development, and provides a mechanism by which the effect is mediated. 相似文献
We tried to characterize the frequency and significance of manifestations of peripheral autonomic insufficiency (PAI) in clinical cases of acute inflammatory demyelinating neuropathies (AIDN). Forty patients with the above diagnosis (21 men and 19 women, 16 to 72 years old) were examined. To detect symptoms attributable to PAI, we used Birkmayer–Vein tables; these data were compared with the results of electroneuromyographic (ENMG) examinations. In 38 and 2 cases, clinical manifestations of AIDN corresponded to the Guillain–Barre and Miller–Fisher syndromes, respectively. According to ENMG data, changes in the peripheral nerves and neuromuscular junctions corresponded to axonopathy, myelinopathy, and a mixed damage (myelinoaxonopathy) in 18 (45%), 14 (35%), and 8 (20%) patients, respectively. The following disturbances in the sphere of autonomic control were observed: orthostatic hypotension, in 28 cases (70%); tachycardia in the resting state, in 24 cases (60%); hypertension in the reclining position, in 16 cases (40%); hypohydrosis of the skin on the limbs, in 18 cases (45%); dyspepsia, in 8 cases (20%), and enuresis, in 3 cases (7.5%). Manifestations of PAI began to be observed in the earliest stage of the disease and were preserved within the period of recovery of the motor functions; they were more intensive in the cases of a severe clinical course of polyneuropathies. The severity of autonomic disorders strictly correlated with the level of axonal degeneration (characterized according to the ENMG data). The treatment used (i.v. injections of immunoglobulin, plasmapheresis, use of vasoactive and neurometabolic drugs) not only improved the state of the motor sphere but also decreased the intensity of PAI symptoms. Thus, in the cases of AIDN not only thick myelinated fibers of the peripheral nerves but also a significant proportion of thin fibers responsible for the control of automatic functions are subjected to damage. PAI is rather frequently observed in patients suffering from AIDN, and the level of its manifestation reflects the severity of the disease and intensity of damage to the peripheral nerves. 相似文献
1. The amyloid ß-peptide (Aß) is involved in the mechanisms of Alzheimer dementia. This paper reviews experimental evidence indicating that Aß exerts profound effects on the regulation of the cerebral circulation.2. Thus, Aß compromises the ability of cerebral endothelial cells to produce vascular relaxing factors, impairs the ability of cerebral blood vessels to maintain adequate flow during hypotension, and attenuates the increases in CBF evoked by enhanced brain activity.3. Studies in transgenic mice overexpressing the amyloid precursor protein suggest that these cerebrovascular alterations disrupt the delicate balance between the brain's energy requirements and cerebral blood supply, rendering the brain more vulnerable to ischemic injury.4. The findings support the recently emerged notion that vascular factors play a pathogenic role in the early stages of Alzheimer dementia. 相似文献