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81.
C. L. Devlin P. J. S. Smith 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1996,166(4):270-277
To determine possible sources of Ca2+ during excitation-contraction coupling in smooth muscle, a vibrating Ca2+-selective electrode was used to measure Ca2+ flux during the process of contraction. The smooth muscle model was the longitudinal muscle of the body wall of a sea cucumberSclerodactyla briareus. Because acetylcholine caused slow contractions of the muscle that were inhibited by Ca2+ channel blockers diltiazem and verapamil in earlier mechanical studies, we chose a vibrating Ca2+-selective electrode as our method to test the hypothesis that acetylcholine may be stimulating Ca2+ influx across the sarcolemma, providing a Ca2+ source during excitation-contraction coupling. Acetylcholine treatment stimulated a net Ca2+ efflux that was both dose and time dependent. We then tested two L-type Ca2+ channel blockers, diltiazem and verapamil, and two non-specific Ca2+ blockers, cobalt (Co2+) and lanthanum (La3+) on acetylcholine-induced Ca2+ flux. All four Ca2+ blockers tested potently inhibited Ca2+ efflux induced by physiological doses of acetylcholine. We propose that the acetylcholine-induced Ca2+ efflux was the result of, first, Ca2+ influx through voltage-sensitive L-type Ca2+ channels, then the rapid extrusion of Ca2+ by an outwardly directed carrier such as the Na–Ca exchanger as suggested by Li+ substitution experiments. The vibrating Ca2+ electrode has provided new insights on the active and complex role the sarcolemma plays in Ca2+ homeostasis and regulating Ca2+ redistribution during excitation-contraction coupling.Abbreviations
ACh
acetylcholine
-
E-C coupling
excitation-contraction coupling
-
LMBW
longitudinal muscle of the body wall 相似文献
82.
Barbara Huisamen Elna Ellis Magdalena van Dyk Amanda Lochner 《Molecular and cellular biochemistry》1996,162(1):1-9
Although it is well-accepted that the phosphatidylinositol signalling transduction pathway, producing inositol-1,4,5-P3 (InsP3) and inositol-1,3,4,5-P4 (InsP4) as second messengers, functions in heart muscle, virtually nothing is known about the roles of the higher inositol polyphosphates such as inositolhexakisphosphate (InsP6). This study demonstrates that InSP6 has the ability to bind intracellularly, with different binding characteristics, to different myocardial membranes. Binding to purified sarcoplasmic reticulum (SR) membranes, purified sarcolemmal (SL) membranes as well as to viable mitochondria were characterized. Binding to all these membranes display high as well as low affinity binding sites, with differing affinities. Kd values of binding to SR were 32 and 383 nM, to SL 61 and 1312 nM, while those of mitochondrial binding were 230 and 2200 nM respectively.InsP4 binding was also investigated and displayed the following characteristics: to SR, one low affinity binding site (Kd = 203 nM) and to SL, a high as well as a low affinity binding site with Kd values of 41 and 2075 nM respectively. Presence of InsP3, the second messenger for SR calcium release, at concentrations of 1 nM, elevated the binding of InsP4 to SR and SL by a mean of 30% and 20% respectively.Fractionation of SR and SL membranes on sucrose density gradients, after solubilization with CHAPS, indicated that InsP6 bound to two separate protein peaks in both these membranes, while InsP4 bound to only one. In SR membranes, InsP4 bound preferentially to a protein separating at high sucrose density while it bound to a protein separating at low sucrose density in SL membranes. 相似文献
83.
H. L. Sudan C. J. Kerry I. R. Mellor S. -K. Choi D. Huang K. Nakanishi P. N. R. Usherwood 《Invertebrate neuroscience : IN》1995,1(2):159-172
The effects of philanthotoxin-343 (PhTX-343; tyrosyl-butanoyl-spermine) and photolabile analogues of this synthetic toxin
on locust (Schistocerca gregaria) skeletal muscle have been investigated using whole muscle preparations (twitch contractions), single muscle fibres (excitatory
postsynaptic currents (EPSCs)) and muscle membrane patches containing single quisqualate-sensitive glutamate receptors (qGluR).
Analogues containing an azido group attached to either the butanoyl side-chain of PhTX-343 or as a substitute for the hydroxyl
moiety of the tyrosyl residue were about 6 fold more potent antagonists than PhTX-343; those with an azido group located at
the distal end of the toxin molecule were generally 2–3 fold less potent than PhTX-343. When these compounds were tested in
subdued light, they were reversible antagonists of the muscle twitch, EPSC and qGluR. When a muscle was irradiated with U.V.
during application of photolabile toxin combined with either neural stimulation of the muscle orl-glutamate application, antagonism of the twitch, EPSC and qGluR was complete and irreversible. 相似文献
84.
BESSESEN, DANIEL H, CONNIE L RUPP AND ROBERT H ECKEL. Dietary fat is shunted away from oxidation, toward storage in obese zucker rats. Obes Res. 1995;3:179–189. Previous measurements of lipoprotein lipase (LPL) activity in adipose tissue (ATLPL) of lean and obese Zucker rats have consistently documented increased activity in obese rats relative to lean. Since LPL is considered to be rate limiting for the delivery of triglyceride fatty acids (TGFA) to muscle and adipose tissue, these data have been used to suggest that the metabolic partitioning of TGFA favors storage over oxidation in obese rats. To document the partitioning of TGFA directly, the fate of 14C labeled oleic acid (42nmols) was fed to lean, obese, and obese Zucker rats fed a hypocaloric diet designed to chronically reduce weight 25% below that of obese controls (reduced-obese). The amount of 14C recovered in CO2 over 6 hours following ingestion was significantly less in obese rats compared to lean (0.45 ± 0.06 vs. 0.88 ± 0.09nmols, p=.0004) and less still in the reduced obese group (0.34 ± 0.06nmols p=.00003). Six hours after ingestion, the quantity of label found in adipose tissue was significantly greater in the obese rats compared to lean (14.51 ± 1.92 vs. 1.38 ± 0.29nmols p<.00001), but was intermediate in the reduced-obese group (9.23 ± 0.98nmols p=.0003). At 2.2 hours there was significantly more label in skeletal muscle of lean rats compared to either obese or reduced-obese (2.33 ± 0.24; 1.35 ± 0.04nmols p=.01; 1.41 ± 0.27nm p=.02). However, at 6 hours these differences between groups were no longer present. These findings Indicate that dietary fat is shunted away from oxidation toward storage in obese Zucker rats. Additionally it appears that there may be a relative block in the oxidation of TGFA that is taken up by skeletal muscle in obese rats. Finally the relative normalization of this partitioning defect in reduced-obese rats is at variance with what was suggested by previous measurements of tissue specific levels of LPL, and suggests an enhanced recirculation of fatty acids from adipose tissue to muscle in reduced-obese rats. This could occur through increased delivery of non-esterified fatty acids (NEFA) to muscle as a result of an increase in net lipolysis. 相似文献
85.
The roles of Ca2+ mobilization in development of tension induced by acetylcholine (ACh, 0.1–100 µM) in swine tracheal smooth muscle strips were studied. Under control conditions, ACh induced a transient increase in free cytosolic calcium concentration ([Ca2+]i) that declined to a steady-state level. The peak increase in [Ca2+]i correlated with the magnitude of tension at each [ACh] after a single exposure to ACh, while the steady-state [Ca2+]i did not. Removal of extracellular Ca2+ had little effect on peak [Ca2+]i but greatly reduced steady-state increases in [Ca2+]i and tension. Verapamil inhibited steady-state [Ca2+]i only at [ACh]<1 µM. After depletion of internal Ca2+ stores by 10 min exposure to ACh in Ca2+-free solution and then washout of ACh for 5 min in Ca2+-free solution, simultaneous re-exposure to ACh in the presence of 2.5 mM Ca2+ increased [Ca2+]i to the control steady-state level without overshoot. The tension attained was the same as control for each [ACh] used. Continuous exposure to successively increasing [ACh] (0.1–100 µM) also reduced the overshoot of [Ca2+]i at 10 and 100 µM ACh, yet tension reached control levels at each [ACh] used. We conclude that the steady-state increase in [Ca2+]i is necessary for tension maintenance and is dependent on Ca2+ influx through voltage-gated calcium channels at 0.1 µM ACh and through a verapamil-insensitive pathway at 10 and 100 µM. The initial transient increase in calcium arises from intracellular stores and is correlated with the magnitude of tension only in muscles that have completely recovered from previous exposure to agonists. 相似文献
86.
Iciar Martinez Bent Dreyer Aasta Agersborg Annick Leroux Gilles Boeuf 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》1995,112(4)
Rearing of 1-year-old Arctic charr (Salvelinus alpinus) at 12°C, as well as the administration of 50 or 75 mgT3/kg feed, accelerated the neonatal to adult fast myosin heavy chain transition, but the effect of temperature was more dramatic than the effect of T3 administration. The endogenous plasma levels of T3 in charrs reared at 12°C were higher than those of analogous groups reared at natural temperature, which in the period under study was between 0.5 and 12°C. As in other species, T3 seemed to play a role in the regulation of the neonatal to adult fast myosin isoform transition by down-regulating the levels of the neonatal and increasing the levels of an adult fast myosin heavy chain. Temperature seemed to accelerate this transition at least, but not only, by inducing an increase in the endogenous levels of T3 in the Arctic charr. 相似文献
87.
To study the physiological role of the creatine kinase/phosphocreatine (CK/PCr) system in cells and tissues with a high and fluctuating energy demand we have concentrated on the site-directed inactivation of the B- and M-CK genes encoding the cytosolic CK protein subunits. In our approach we used homologous recombination in mouse embryonic stem (ES) cells from strain 129/Sv. Using targeting constructs based on strain 129/Sv isogenic DNA we managed to ablate the essential exons of the B-CK and M-CK genes at reasonably high frequencies. ES clones with fully disrupted B-CK and two types of M-CK gene mutations, a null (M-CK–) and leaky (M-CK1) mutation, were used to generate chimaeric mutant mice via injection in strain C57BL/6 derived blastocysts. Chimaeras with the B-CK null mutation have no overt abnormalities but failed to transmit the mutation to their offspring. For the M-CK– and M-CK1 mutations successful transmission was achieved and heterozygous and homozygous mutant mice were bred. Animals deficient in MM-CK are phenotypically normal but lack muscular burst activity. Fluxes through the CK reaction in skeletal muscle are highly impaired and fast fibres show adaptation in cellular architecture and storage of glycogen. Mice homozygous for the leaky M-CK allele, which have 3-fold reduced MM-CK activity, show normal fast fibres but CK fluxes and burst activity are still not restored to wildtype levels. 相似文献
88.
E. R. Chin H. J. Green F. Grange J. D. Mercer P. J. O'Brien 《Molecular and cellular biochemistry》1994,139(1):41-52
A multiple measurement system for assessing sarcoplasmic reticulum (SR) Ca++-ATPase activity and Ca++-uptake was used to examine the effects of SR fractionation and quick freezing on rat white (WG) and red (RG) gastrocnemius muscle.In vitro measurements were performed on whole muscle homogenates (HOM) and crude microsomal fractions (CM) enriched in SR vesicles before and after quick freezing in liquid nitrogen. Isolation of the CM fraction resulted in protein yields of 0.96±0.1 and 0.99±0.1 mg/g in WG and RG, respectively. The percent Ca++-ATPase recovery for CM compared to HOM was 14.5% (WG) and 10.1% (RG). SR Ca++-activated Ca++-ATPase activity was not affected by quick freezing of HOM or CM, but basal ATPase was reduced (P<0.05) in frozen HOM (5.12±0.18–3.98±0.20 mole/g tissue/min in WG and from 5.39±0.20–4.48±0.24 mole/g tissue/min in RG). Ca++-uptake was measured at a range of physiological free [Ca++] using the Ca++ fluorescent dye Indo-1. Maximum Ca++-uptake rates when corrected for initial [Ca++]f were not altered in HOM or CM by quick freezing but uptake between 300 and 400nM free Ca++ was reduced (P<0.05) in quick frozen HOM (1.30±0.1–0.66±0.1 mole/g tissue/min in WG and 1.04±0.2–0.60±0.1 mole/g tissue/min in RG). Linear correlations between Ca++-uptake and Ca++-ATPase activity measured in the presence of the Ca++ ionophore A23187 were r=+0.25, (P<0.05) and r=+0.74 (P<0.05) in HOM and CM preparations, respectively, and were not altered by freezing. The linear relationships between HOM and CM maximum Ca++-uptake (r=+0.44, P<0.05) and between HOM and CM Ca++-ATPase activity (r=+0.34, P<0.05) were also not altered by tissue freezing. These data suggest that alterations in maximal SR Ca++-uptake function and maximal Ca++-ATPase activity may be measured in both HOM and CM fractions following freezing and short term storage. (Mol Cell Biochem139, 41–52, 1994) 相似文献
89.
Sajal Chakraborti Sandip K. Batabyal John R. Michael Tapati Sanyal 《Molecular and cellular biochemistry》1994,130(2):121-127
Exposure of rabbit pulmonary arterial smooth muscle cells to 10 M of the calcium ionophore A23187 dramatically stimulates cell membrane-associated phospholipase A2 activity and arachidonic acid release. In addition, A23187 also enhances cell membrane-associated serine esterase activity. Serine esterase inhibitors phenylmethylsulfonylfuoride and diisopropyl fluorophosphate prevent the increase in serine esterase and phospholipase A2 activities and arachidonic acid release caused by A23187. A23187 still stimulated serine esterase and phospholipase A2 activities and arachidonic acid release in cells pretreated with nominal Ca2+ free buffer. Treatment of the cell membrane with A23187 does not cause any appreciable change in serine esterase and phospholipase A2 activities. Pretreatment of the cells with actinomycin D or cycloheximide did not prevent the increase in the cell membrane associated serine esterase and phospholipase A2 activities, and arachidonic acid release caused by A23187. These results suggest that (i) a membrane-associated serine esterase plays an important role in stimulating the smooth muscle cell membrane associated phospholipase A2 activity (ii) in addition to the presence of extracellular Ca2+, release of Ca2+ from intracellular storage site(s) by A23187 also appears to play a role in stimulating the cell membrane-associated serine esterase and phospholipase A2 activities, and (iii) the increase in the cell membrane-associated serine esterase and phospholipase A2 activities does not appear to require new RNA or protein synthesis.Abbreviations A23187
calcium ionophore
- AA
arachidonic acid
- PMSF
phenylmethyl sulfonylfuoride
- DFP
diisopropyl-fluorophosphate
- DMEM
Dulbecco's modified Eagles medium
- FCS
fetal calf serum
- PBS
phosphate buffered saline
- HBPS
Hank's buffered physiological saline
- PLA2
phospholipase A2 相似文献
90.