Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myothermal measurements of tension-independent heat are used to calculate the quantity of calcium released during isometric contraction and the rate at which it is removed in control, thyrotoxic and pressure-overloaded rabbit hearts. Experiments were carried out at 30 degrees C. In control rabbit hearts 41.0 +/- 7.0 nmoles/g Ca++ was released into the cytosol for each beat, while the rate at which the Ca++ was removed from the cytosol was 24.4 +/- 4.4 nmoles/g sec. In the presence-overloaded preparations, the amount of calcium released and the rate of calcium removal were 41% and 40% of control values. This reduction was correlated with the mRNA levels for the sarcoplasmic reticulum (SR) Ca++ ATPase, phospholamban and the ryanodine receptor. The depression was also correlated with a reduction in SR Ca++ ATPase protein expression. In thyrotoxic hearts compared with controls, with each activation there is an increase in the amount of calcium liberated into the cytosol (39%) and the rate of calcium removal (31%). This increase is correlated with an increase in the mRNA and protein expression for the SR Ca++ ATPase as well as the mRNA for the ryanodine receptor. Calsequestrin mRNA was unchanged in all of the experimental preparations. It is suggested that the alteration in the calcium cycling proteins offers at least a partial explanation for the changes in calcium cycling measured in response to the stresses applied.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The regulation of calcium cycling in stressed hearts. 133 66

The involvement of Ca release from intracellular stores in the induction of long-term depression and depotentiation of excitatory synaptic transmission was investigated in the rat dentate gyrus using dantrolene, an agent known to block Ca release via the ryanodine receptor. In control slices, low-frequency stimulation (1 Hz for 15 min) induced robust long-term depression of baseline field excitatory postsynaptic potentials and depotentiation of previously established long-term potentiation. Dantrolene (50 microM) was found to block completely both long-term depression of baseline responses and depotentiation. Moreover, long-term potentiation induced by high-frequency stimulation was enhanced in the presence of dantrolene.
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PMID:Dantrolene inhibits long-term depression and depotentiation of synaptic transmission in the rat dentate gyrus. 857 62

1. Primary-cultured cerebellar Purkinje cells (PCs) from mouse embryos were whole cell voltage clamped, and L-glutamate (Glu) was applied iontophoretically to the dendrite. Long-term depression (LTD) of Glu-evoked currents was induced through the conjunction of repeated depolarizations and Glu applications. 2. Thapsigargin, a specific inhibitor of Ca(2+)-ATPase on the endoplasmic reticulum, and ryanodine and ruthenium red, inhibitors of the ryanodine receptor, blocked the induction of LTD. 3. Thapsigargin and ryanodine alone did not affect influx of Ca2+ through voltage-gated Ca2+ channels and inward currents evoked by Glu applications. 4. Our results suggest that Ca2+ release from internal stores, particularly from ryanodine-sensitive stores, is necessary for the induction of LTD in cultured PCs.
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PMID:Ca2+ release from Ca2+ stores, particularly from ryanodine-sensitive Ca2+ stores, is required for the induction of LTD in cultured cerebellar Purkinje cells. 859 7

NO donors were found to reduce the rate of Ca2+ release from isolated skeletal muscle sarcoplasmic reticulum (SR) and the open probability of single ryanodine receptor Ca2+ release channels (RyRCs) in planar lipid bilayers, and these effects were prevented by the NO quencher hemoglobin and reversed by 2-mercaptoethanol. Ca2+ release assessed in skeletal muscle homogenates was also reduced by NO that was generated in situ from L-arginine by endogenous, nitro-L-arginine methylester-sensitive NO-synthase. The effect of NO on the RyRC might explain NO-induced depression of contractile force in striated muscles and, since both RyRC isoforms and NOS isoenzymes aer ubiquitous, may represent a wide-spread feedback mechanism in Ca2+ signaling; i.e. Ca-dependent activation of NO production and NO-evoked reduction of Ca2+ release from intracellular Ca2+ stores.
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PMID:Inhibition of the skeletal muscle ryanodine receptor calcium release channel by nitric oxide. 860 45

Studies have suggested that an increase in intracellular [Ca2+] is necessary for the induction of both long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission, and that release of Ca2+ from intracellular storage pools can be necessary to induce LTP. We investigated whether release of Ca2+ from intracellular stores also is required for the induction of LTD at Schaffer collateral-CA1 synapses in hippocampal slices. Both thapsigargin (1 microM) and cyclopiazonic acid (1 microM), compounds that deplete all intracellular Ca2+ pools by blocking LTP-dependent Ca2+ uptake into intracellular compartments, blocked the induction, but not maintenance, of LTD by low-frequency stimulation (LFS) (1 Hz/15 min) without affecting baseline synaptic transmission. Washout of the reversible inhibitor cyclopiazonic acid restored the ability to induce LTD. In contrast, thapsigargin did not block depotentiation of LTP by 1 Hz LFS, suggesting that LTP causes a reduction in the threshold [Ca2+] necessary for LTD. Selective depletion of the ryanodine receptor-gated Ca2+ pool by bath application of ryanodine (10 microM) also blocked the induction of LTD, indicating a requirement for Ca(2+)-induced Ca2+ release. Impalement of CA1 pyramidal neurons with microelectrodes containing thapsigargin (500 nM to 200 microM) prevented the induction of LTD at synapses on that neuron without blocking LTD in the rest of the slice. In contrast, similar filling of CA1 pyramidal neurons with ryanodine (2 microM to 5 mM) did not block the induction of LTD. From these data, we conclude that the induction of LTD requires release of Ca2+ both from a presynaptic ryanodine-sensitive pool and from postsynaptic (presumably IP3-gated) stores.
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PMID:Induction of hippocampal long-term depression requires release of Ca2+ from separate presynaptic and postsynaptic intracellular stores. 881 77

1. Effects of xanthone and its derivative, 1,3,6,7-tetrahydroxyxanthone (norathyriol), on Ca2+ release and ryanodine binding were studied in isolated sarcoplasmic reticulum (SR) vesicles from rabbit skeletal muscle. 2. Both xanthone and norathyriol dose-dependently induced Ca2+ release from the actively loaded SR vesicles which was blocked by ruthenium red, a specific Ca2+ release inhibitor, and Mg2+. 3. Xanthone and norathyriol also dose-dependently increased apparent [3H]-ryanodine binding. Norathyriol, but not xanthone, produced a synergistic effect on binding activation when added concurrently with caffeine. 4. In the presence of Mg2+, which inhibits ryanodine binding, both caffeine and norathyriol, but not xanthone, could restore the binding to the level observed in the absence of Mg2+. 5. Xanthone activated the Ca(2+)-ATPase activity of isolated SR vesicles dose-dependently reaching 70% activation at 300 microM. 6. When tested in mouse diaphragm, norathyriol potentiated the muscle contraction followed by twitch depression and contracture in either a Ca(2+) -free bathing solution or one containing 2.5 mM Ca2+. These norathyriol-induced effects on muscle were inhibited by pretreatment with ruthenium red or ryanodine. 7. These data suggest that xanthone and norathyriol can induce Ca2+ release from the SR of skeletal muscle through a direct interaction with the Ca2+ release channel, also known as the ryanodine receptor.
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PMID:Induction of calcium release from sarcoplasmic reticulum of skeletal muscle by xanthone and norathyriol. 884 39

1. The induction of long-term potentiation (LTP) was investigated in the rat dentate gyrus in the presence of ryanodine, an agent which is known to selectively bind to the ryanodine receptor (RyR) Ca2+ channels which regulate Ca2+ release from intracellular Ca2+ stores. 2. In control media, high frequency stimulation (HFS) induced LTP, and prolonged low frequency stimulation (LFS) induced long-term depression (LTD), of field excitatory postsynaptic potentials (EPSPs) and patch clamped excitatory postsynaptic currents (EPSCs). 3. In the presence of ryanodine, at a threshold concentration of about 1 microM, HFS-induced LTP was inhibited, whereas LFS (5 Hz, 900 pulses) now induced LTP. 4. The N-methyl-D-aspartate receptor (NMDAR) antagonist D-2-amino-phosphonopentanoate (D-AP5), at both 50 and 200 microM, did not prevent the induction of LTP by 5 Hz LFS in the presence of ryanodine. This demonstrates the NMDAR independence of LTP induction in the presence of ryanodine. Furthermore, D AP5 reversed the block of HFS-induced LTP by ryanodine. 5. The induction of LTP by 5 Hz LFS in the presence of ryanodine was blocked by lowering extracellular Ca2+, or by rapidly buffering intracellular Ca2+ to very low levels with BAPTA. 6. The induction of LTP by 5 Hz LFS was inhibited by the L-type voltage-gated Ca2+ channel blocker nifedipine, and also by Ni2+ a commonly used T type voltage-gated Ca2+ channel blocker. 7. The 5 Hz LFS-induced LTP in the presence of ryanodine was inhibited by the metabotropic glutamate receptor (mGluR) antagonist (+)-alpha-methyl 4-carboxyphenylglycine (MCPG). 8. The 5 Hz LFS-induced LTP in the presence of ryanodine was blocked by Ruthenium Red, an agent known to block RyR channel opening, and also by thapsigargin, an agent known to block-ATP-dependent Ca2+ uptake into endoplasmic reticulum. 9. The results of the present studies emphasize the importance of intracellular Ca2+ stores in the induction of LTP.
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PMID:Ryanodine produces a low frequency stimulation-induced NMDA receptor-independent long-term potentiation in the rat dentate gyrus in vitro. 888 81

The effects of PCBs on hippocampal function were studied in vitro, by radioligand-receptor binding analysis and electrophysiological measurements of the hippocampal slice preparation. [3H]Ryanodine, a conformation-sensitive probe for ryanodine receptors, was employed to determine how PCBs influence specific high-affinity occupancy to receptors found in microsomes isolated from rat hippocampus. PCB 95 (2,2',3,5'6-pentachlorobiphenyl) exhibited a dose-dependent enhancement of [3H]ryanodine receptor occupancy with an EC50 of 12 microM. In contrast, PCB 66 (2,3'4,4'-tetrachlorobiphenyl) showed no activity toward ryanodine receptors, up to its solubility limit (> or = 200 microM. Population spike (PS) and excitatory postsynaptic potential (EPSP) responses were recorded from striatum pyramidale of the CA1 region, which were generated from single pulse orthodromic stimulation of Schaffer collateral/commissural (SC/C) fibers at striatum radiatum of the hippocampal slice preparation. After the introduction of PCB 95 to the perfusion medium, PCB 95 depressed PS amplitude, especially at high stimulus intensities. Significant reductions in PS and EPSP maxima were seen, even after induction of long term potentiation, a model of neuroplasticity. However, these actions were not observed with PCB 66 which lacks ryanodine receptor activity, implicating a ryanodine receptor-mediated mechanism in the general depression of pyramidal cell excitability seen with PCB 95. Taken together, these results reveal a novel, arylhydrocarbon (Ah) receptor-independent, mechanism by which PCB 95 alters neuronal Ca2+ signaling and neuroplasticity in adult brain.
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PMID:Ortho-substituted 2,2',3,5',6-pentachlorobiphenyl (PCB 95) alters rat hippocampal ryanodine receptors and neuroplasticity in vitro: evidence for altered hippocampal function. 929 93

1. Presynaptic injection of cyclic ADP-ribose (cADPR), a modulator of the ryanodine receptor, increased the postsynaptic response evoked by a presynaptic spike at an identified cholinergic synapse in the buccal ganglion of Aplysia californica. 2. The statistical analysis of long duration postsynaptic responses evoked by square depolarizations of the voltage-clamped presynaptic neurone showed that the number of evoked acetylcholine (ACh) quanta released was increased following cADPR injection. 3. Overloading the presynaptic neurone with cADPR led to a transient increase of ACh release followed by a depression. 4. cADPR injections did not modify the presynaptic Ca2+ current triggering ACh release. 5. Ca2+ imaging with the fluorescent dye rhod-2 showed that cADPR injection rapidly increased the free intracellular Ca2+ concentration indicating that the effects of cADPR on ACh release might be related to Ca2+ release from intracellular stores. 6. Ryanodine and 8-amino-cADPR, a specific antagonist of cADPR, decreased ACh release. 7. ADP-ribosyl cyclase, which cyclizes NAD+ into cADPR, was present in the presynaptic neurone as shown by reverse transcriptase-polymerase chain reaction experiments. 8. Application of NAD+, the substrate of ADP-ribosyl cyclase, increased ACh release and this effect was prevented by both ryanodine and 8-amino-cADPR. 9. These results support the view that Ca(2+)-induced Ca2+ release might be involved in the build-up of the Ca2+ concentration which triggers ACh release, and thus that cADPR might have a role in transmitter release modulation.
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PMID:Cyclic ADP-ribose and calcium-induced calcium release regulate neurotransmitter release at a cholinergic synapse of Aplysia. 951 1

Ca2+ released from presynaptic and postsynaptic intracellular stores plays important roles in activity-dependent synaptic plasticity, including long-term depression (LTD) of synaptic strength. At Schaffer collateral-CA1 synapses in the hippocampus, presynaptic ryanodine receptor-gated stores appear to mobilize some of the Ca2+ necessary to induce LTD. Cyclic ADP-ribose (cADPR) has recently been proposed as an endogenous activator of ryanodine receptors in sea urchin eggs and several mammalian cell types. Here, we provide evidence that cADPR-mediated signaling pathways play a key role in inducing LTD. We show that biochemical production of cGMP increases cADPR concentration in hippocampal slices in vitro, and that blockade of cGMP-dependent protein kinase, cADPR receptors, or ryanodine-sensitive Ca2+ stores each prevent the induction of LTD at Schaffer collateral-CA1 synapses. A lack of effect of postsynaptic infusion of either cADPR antagonist indicates a probable presynaptic site of action.
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PMID:Evidence of a role for cyclic ADP-ribose in long-term synaptic depression in hippocampus. 1009 63


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