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991.
We used the whole-cell patch-clamp method to investigate the voltage dependence of the L-type Ca current (I Ca,L) and intracellular Ca (Cai) transient in ventricular myocytes isolated from the rat heart. Intracellular Ca was monitored using Fura-2 and the experiments were carried out at 36° C. We measured I Ca,L by using a caesium-based internal dialysis solution to eliminate interfering K currents. The voltage dependence of peak I Ca,L amplitude was bell-shaped: I Ca,L was maximal at +10 mV and declined at more positive potentials. When I Ca,L was integrated over the first 25 ms to estimate the magnitude of Ca entry, this had a very similar voltage dependence to peak I Ca,L. In all cells, phasic Fura-2 transients were abolished by 5 μM ryanodine (a blocker of the sarcoplasmic reticulum, SR) showing that the Fura-2 transient provided an index of the magnitude of SR Ca release. For experiments measuring the Cai transient, we used a K-based internal dialysis solution to preserve normal excitation-contraction coupling. In 30–40% of cells, we found that the Fura-2 transient had a bell-shaped voltage dependence. This suggests that, in these cells, the primary trigger mechanism for Ca-induced Ca-release might have been Ca entry via I Ca,L. In the remaining 60–70% of cells, the voltage dependence of the Fura-2 transient was not bell-shaped. The Fura-2 transient reached a maximum with a pulse to +10 mV, and the amplitude of the transient did not decline significantly at more positive potentials to this. In cells with a non-bell-shaped voltage dependence of the Fura-2 transient, pulses to potentials as far positive as +140 mV elicited phasic Fura-2 transients. Since this potential exceeded the Nernst potential for Ca, it was unlikely there was any tigger Ca entry via I Ca,L at this potential. This would suggest that, in these cells, another trigger for SR Ca release (in addition to I Ca,L) might be present. We conclude that rat ventricular myocytes, produced using a standard isolation technique and under standard recording conditions, can show either a bell-shaped or a sigmoidal voltage dependence of the Fura-2 transient. Received: 13 October 1995/Received after revision and accepted: 10 January 1996  相似文献   
992.
Heat production and isovolumetric pressure development (P) were measured simultaneously in the arterially perfused rat ventricle. The time course of the calorimetric signal that follows a contraction could be decomposed into four components of energy released. Three of these components (H1, H2, and H4) were pressure independent, only H3 correlated with either P or the pressure-time integral (PtI) (r>0.78, n=36, P<0.01). The dimensionless slope of the regression of H3 on P was 0.24 (an index of muscle economy) and the absence of O2 (N2 replacement) decreased it to 0.178 suggesting that 26% of H3 is related to oxidative metabolism. H4 was the most affected by the lack of O2 in the perfusate. It decreased to 16% in the first beat under N2 without change in P or in H1, H2 or H3, and disappeared (1.6±1.0 mJ.g–1) in the fourth contraction under N2 (while P, H1, H2 and H3 remained over 64% of their control values). H4 was activated during the first 1–3 beats after a quiescent period and remained active for several seconds (even in the absence of subsequent stimulation) as if the basal metabolism had been increased to a new steady level. H1 and H2 were dependent on the extracellular Ca. The magnitudes of both H1 (1.8±0.2 mJ.g–1) and H2 (2.7±0.2 mJ.g–1) were similar to those reported for the fast and slow components of activation heat in skeletal muscle. If twin stimuli are applied (200 ms apart), additional energy is released (+3.0±0.3 mJ.g–1) that can be decomposed in two components similar to those identified as H2 and H3. The magnitude of H1, its absence in the twin contraction and its Ca dependency suggest an association with Ca-binding processes (mainly Troponin C). The presence of an H2 component during the twin contraction, its magnitude and Ca dependence gives support to a relationship between H2 and Ca removal processes.  相似文献   
993.
Summary The short-latency DR-EPSPs resistant to Ca2+-lack and to addition of Mn2+ and Mg2+ result from electrical coupling between primary afferents and spinal motoneurons in frogs and toads. There are two time constants by which the time constant for the decay of the electrotonic DR-EPSP can be described: 1. the membrane time constant which determines the rate of passive decay of the membrane potential shift produced directly by the presynaptic spike, 2. the rate at which the presynaptic after-depolarization (ADP) declines. The latter value is very large as compared with the postsynaptic membrane time constant. Presynaptic tetanization does not change the magnitude of the initial spike-induced component of the EPSP but its later slowly decaying portion is potentiated markedly as a result of the post-tetanic increase in the amplitude of the ADP. The perfusion with substances blocking potential dependent potassium channels (4-AP and TEA) greatly augments the DR-EPSP due to prolongation of the presynaptic spike and appearance of multiple discharges in the presynaptic fibers. An antidromic electrical coupling between motoneurons and the terminals of primary afferents was demonstrated in the isolated amphibian spinal cord perfused with zero Ca2+, 2 mM Mn2+ solution containing TEA or 4-AP. Under these conditions ventral root volleys may evoke local graded depolarizing potentials in some sensory fibers. Such antidromic coupling potentials can reach the critical level for generating a single or multiple discharge.  相似文献   
994.
Summary Slow phase horizontal eye movements, elicited by the vestibulo-ocular reflex (VOR) and/or visual pursuit (VP) systems, were examined in normal children (NC, 9–16 years) and normal adults (NA). At slow frequencies of sinusoidal stimulation of the body (with the head immobilized) and/or of a visual target, the NC (9–12 years) exhibited (a) immature VP and VOR Suppression and mature VOR Enhancement in the presence of a visual image; (b) immature VOR Suppression and mature VOR Enhancement in the presence of a non-visual image of the spatial location of a visual target, an extra-retinal signal; (c) inability to augment or depress the VOR gain with a non-visual image; (d) mature VOR Suppression ratios; and (e) adjustment of VOR gain to a high value. The maturational process was featured by (a) parallel development of VP and VOR Suppression; (b) modification of the VOR gain; and (c) an increasing ability to augment or depress the VOR with a non-visual image. The observations in NC (9–12) are ascribed to a maturational lag of an extra-retinal process interacting with mature retinal and vestibular processes and, hence, suggest that both the retinal and vestibular contributions to ocular stability predate the development of an extra-retinal signal. When mature, the central nervous system utilizes both extra-retinal and retinal signals to mediate adaptive regulation of VOR gain and to preserve stable visual pursuit motion and VOR Suppression. Our findings also suggest that during tasks requiring visual-vestibular interaction, VP and VOR mechanisms appear to be indirectly rather than directly coupled.Supported in part by a grant from the Rehabilitation Services Administration, H.E.W. (23-P555-18/3)  相似文献   
995.
Introduction: Sphingolipids belong to a complex class of lipid molecules that are crucially involved in the regulation of important biological processes including proliferation, migration and apoptosis. Given the significant progress made in understanding the sphingolipid pathobiology of several diseases, sphingolipid-related checkpoints emerge as attractive targets. Recent data indicate the multifaceted contribution of the sphingolipid machinery to osteoclast – osteoblast crosstalk, representing one of the pivotal interactions underlying bone homeostasis. Imbalances in the interplay of osteoblasts and osteoclasts might lead to bone-related diseases such as osteoporosis, rheumatoid arthritis, and bone metastases.

Areas covered: We summarize and analyze the progress made in bone research in the context of the current knowledge of sphingolipid-related mechanisms regulating bone remodeling. Particular emphasis was given to bioactive sphingosine 1-phosphate (S1P) and S1P receptors (S1PRs). Moreover, the mechanisms of how dysregulations of this machinery cause bone diseases, are covered.

Expert opinion: In the context of bone diseases, pharmacological interference with sphingolipid machinery may lead to novel directions in therapeutic strategies. Implementation of knowledge derived from in vivo animal models and in vitro studies using pharmacological agents to manipulate the S1P/S1PRs axes suggests S1PR2 and S1PR3 as potential drug targets, particularly in conjunction with technology for local drug delivery.  相似文献   

996.
997.
998.
Intracellular Ca2+ transients were recorded from frog twitch muscle fibres in response to voltage-clamp depolarizing pulses, using arsenazo III as an intracellular Ca2+ indicator. The effect of the activation of protein kinase C (PKC) on the Ca2+ transients was studied. With 1 M phorbol 12,13-dibutyrate (PDBu), a PKC activator, the peak of the Ca2+ transients increased to about 120% of control during the first 0.5 h, and then decreased gradually to a plateau of 44% of control within the following 2 h. This effect of PDBu could be alleviated significantly by PKC inhibitors, 10 M polymyxin B (PMB) or 30 M 1-(5-isoquinolinylsulphonyl)-2-methyl-piperazine (H-7). Moreover, PDBu caused an upward shift of the strength/duration curve. In Li+-loaded muscle fibres the Ca2+ transients could not fully recover after 80 mM K+ exposure for 15 min, while the post-K+ Ca2+ transients could be completely restored in the fibres not loaded with Li+. In the presence of 10 M PMB or 30 M H-7, a full restoration of the post-K+ Ca2+ transients was seen in Li+-loaded fibres. PMB supplemented after high-K+ exposure also could result in a complete recovery of the post-K+ Ca2+ transients in Li+-loaded fibres. The role of PKC in modulating excitation-contraction coupling in frog twitch muscle fibres is clearly indicated, but the mechanism(s) and physiological significance remain to be established.  相似文献   
999.
Excitation–contraction coupling was characterized in enzymatically isolated adult honeybee skeletal muscle fibers. The voltage-dependent Ca2+ current (I Ca) underlies action potential (AP) depolarization phase in honeybee muscle. A single AP leads to rapid and transient cytoplasmic Ca2+ increase (“Ca2+ transient”), which afterwards returns toward baseline following an exponential time course. Trains of APs elicit a staircase increase of Ca2+, as a result of multiple Ca2+ transient summation. Surprisingly, the nifedipine-sensitive I Ca is blocked by allethrin, a pyrethroid insecticide, revealing myotoxic effects of this neurotoxic insecticide for honeybees. Ca2+ transients are under the control of Ca2+ entry through voltage-activated Ca2+ channels. Indeed, Ca2+ transient amplitude depends on extracellular Ca2+ concentration, and bell-shaped relationships are obtained for both I Ca integral and the Ca2+ transient peak in response to depolarizations of increasing amplitude. The slow inactivation kinetics of I Ca induces long-lasting Ca2+ transients that tend to reach a plateau and to return toward a resting level after the end of the stimulation. A Ca2+-induced Ca2+ release mechanism is suggested by two results. First, caffeine (≥5 mM) and 4-cmc (>0.4 mM), two activators of the sarcoplasmic reticulum Ca2+ release channels (CRCs), induce Ca2+ elevations in the absence of extracellular Ca2+. Second, ryanodine (5 μM) a plant alkaloid that binds specifically to CRCs, depresses voltage-induced Ca2+ transients. Honeybee muscle fibers represent a valuable model to study invertebrate excitation–contraction coupling and insecticide myotoxicity toward useful insects.  相似文献   
1000.
PS‐b‐PMMA copolymers and blends of PS and PMMA were analyzed by the online coupling of LC at the critical point of adsorption and 1H NMR. The separation of the polymers was carried out at chromatographic conditions which correspond to the critical point of PMMA and the size exclusion mode of PS. It was shown that blends of PS and PMMA homopolymers could be well separated at critical conditions of PMMA. The analysis of both the copolymers and the blends were carried out by online coupled 1H NMR. The block copolymers were analyzed with respect to the chemical composition. LCCC‐NMR coupling was allowed to determine the individual blocks of the copolymers regarding molar mass. The data were compared with the separation at critical conditions of PS.

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