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Query: UMLS:C0848283 (rundown)
 502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Ca2+ imaging and simultaneous intracellular recording were performed on CA3 pyramidal neurons in hippocampal slice cultures and standard acute slices. Both fura-2 and a dextran conjugate of fura-2 (MW = 10,000) were used in the Ca2+ measurements to control for compartmentalization artifacts. Experiments were performed under conditions giving minimal ligand- and voltagegated Ca2+ influx, with the use of competitive and noncompetitive antagonists of ionotropic glutamate receptors and steady-state depolarization, respectively. 2. Tetanic stimulation of stratum lucidum evoked dendritic Ca2+ transients with rapid onset that were blocked by the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (2-5 microM), but not by the competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10-50 microM). Zn(2+)-containing mossy fiber terminals (assessed by Timm's staining) and postsynaptic structures (thorny excrescences) are preserved in s. lucidum of hippocampal slice cultures. 3. A Ca2+ store loading protocol, consisting of brief repolarizations followed by steady depolarization, primed most of the neurons so that a subsequent tetanus gave a Ca2+ increase in the presence of MK-801 that was reported by both fura-2 and the dextran conjugate. The onset of the Ca2+ increase was significantly delayed (by 2-3 s) with respect to the MK-801-sensitive increase, and often had a different spatial pattern within the neuron. Response characteristics were similar in slice cultures and acute slices. 4. The delayed Ca2+ increase showed a steep rundown with subsequent stimuli, but was restored by further priming by the Ca2+ store loading paradigm. Postsynaptic currents evoked by the tetani under these conditions were not correlated with the magnitude of the delayed Ca2+ transients. 5. Delayed Ca2+ increases were observed in 44% of the neurons dialyzed with normal intracellular solution at room temperature. The success rate of observing delayed Ca2+ transients was increased to 86% in neurons maintained at 30 degrees C, and dialyzed with an inhibitor of the inositol-triphosphate-3-kinase. 6. The delayed Ca2+ transients could not be initiated after inhibition of endosomal Ca(2+)-ATPase-mediated uptake by thapsigargin. 7. Both fura-2 and the dextran conjugate reported increases in resting Ca2+ levels after the loading protocols, that were absent after priming in thapsigargin, and decreases in resting Ca2+ levels after successive tetani in MK-801, suggesting that the Ca2+ changes were largely cytosolic. 8. The present results support the hypothesis that these synaptically mediated, delayed Ca2+ transients represent release from intracellular Ca2+ stores that can be loaded and depleted repeatedly, and are evoked by presynaptic release of endogenous neurotransmitter.
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PMID:Ca2+ release from intracellular stores induced by afferent stimulation of CA3 pyramidal neurons in hippocampal slices. 883 43

Glutamate responses in cultured rat astrocytes from cerebella of neonatal rats were investigated using the perforated-patch configuration to record membrane currents without rundown of intracellular messenger cascades, and microfluorometric measurements to measure the intracellular Ca2+ concentration ([Ca2+]i) and intracellular pH (pHi) with fura-2 AM and 2',7'-bis-(2-carboxyethyl)-5,6-carboxyfluorescein acetoxy methylester respectively. In the perforated-patch mode, glutamate evoked single or multiple outward current transients in 82% of the cells, which disappeared when the recording technique was converted into a conventional whole-cell mode. The outward current transients were accompanied by [Ca2+]i transients, whereas pHi fell monophasically, without any sign of oscillation. Pharmacological analysis of the glutamate-induced responses indicated that ionotropic receptor activation evoked an inward current but no outward current transients, and metabotropic receptor activation (of the mGluR1/5 type) elicited outward current transients but no inward current. The outward current transients were reduced in frequency, or even abolished, after depletion of the intracellular Ca2+-stores by the Ca2+-ATPase inhibitor cyclopiaconic acid (10 microM). They reversed near -85 mV and were reduced by tetraethylammonium (10 mM), suggesting that they were caused by K+ channel activation. It is concluded that glutamate evoked these K+ outward current transients by oscillatory Ca2+ release mediated by mGluR activation. The corresponding membrane potential waves across the astroglial syncytium could provide spatial and temporal dynamics to the glial K+ uptake capacity and other voltage-dependent processes.
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PMID:Intracellular calcium transients and potassium current oscillations evoked by glutamate in cultured rat astrocytes. 929 74

Using whole-cell patch-clamp recording of acutely isolated rat hippocampal CA1 neurons, we studied the state-dependent cross-inhibition between anionic GABA(A) and glycine (Gly) ionotropic receptors. Co-application of relatively high concentrations of GABA and Gly produced a total current (IGABA + Gly) much smaller than the linear summation of the two individual responses. The mutual inhibition between IGABA and IGly was voltage-independent. However, no current inhibition was observed with co-application of low concentrations of these two agonists. The hippocampal neurons lacking Gly response (IGly) showed no current inhibition with GABA current (IGABA), whereas the neurons losing GABA response (IGABA) (after complete rundown of IGABA) showed no current inhibition with IGly. The current inhibition was also absent in the presence of Gly or GABA(A) receptor antagonists, strychnine or bicuculline, respectively. The results indicate that cross-inhibition between GABA(A) and Gly receptors is state-dependent and a direct receptor-receptor interaction might enable the cross-inhibition to occur.
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PMID:State-dependent cross-inhibition between anionic GABA(A) and glycine ionotropic receptors in rat hippocampal CA1 neurons. 1189 14

Agonists of kainate receptors (KARs) cause both the opening of the associated ion channels and the activation of signalling pathways driven by G-proteins and PKC. Here we report the existence of an unknown mechanism of KAR autoregulation, involving the interplay of this two signalling mechanisms. Repetitive activation of native KARs evoked the rundown of the ionotropic responses in a manner that was dependent on the activation of PKC. Experiments on recombinant GluR5 expressed in neuroblastoma cells indicated that KARs trigger the activation of PKC and induce the internalization of membrane receptors. This phenomenon depends on the PKC-mediated phosphorylation of serines 879 and 885 of the GluR5-2b subunits, since mutation of these two residues abolished internalization. These results reveal that the non-canonical signalling of KARs is associated with a sensitive mechanism that detects afferent activity. Such a mechanism represents an active way to limit overactivation of the KAR system, by regulating the number of KARs in the cell membrane.
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PMID:PKC-dependent autoregulation of membrane kainate receptors. 1789 3

The P2X(1) receptor-channels activated by extracellular ATP contribute to the neurogenic component of smooth muscle contraction in vascular beds and genitourinary tracts of rodents and humans. In the present study, we investigated the interactions of plasma membrane phosphoinositides with P2X(1) ATP receptors and their physiological consequences. In an isolated rat mesenteric artery preparation, we observed a strong inhibition of P2X(1)-mediated constrictive responses by depletion of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] with the phosphatidylinositol 4-kinase inhibitor wortmannin. Using the Xenopus laevis oocyte expression system, we provided electrophysiological evidence that lowering PI(4,5)P(2) levels with wortmannin significantly decreases P2X(1) current amplitude and recovery. Previously reported modulation of recovery of desensitized P2X(1) currents by phospholipase C-coupled 5-hydroxytryptamine(2A) metabotropic receptors was also found to be wortmannin-sensitive. Treatment with wortmannin alters the kinetics of P2X(1) activation and inactivation without changing its sensitivity to ATP. The functional impact of wortmannin on P2X(1) currents could be reversed by addition of intracellular PI(4,5)P(2), but not phosphatidylinositol 3,4,5-trisphosphate, and direct application of PI(4,5)P(2) to excised inside-out macropatches rescued P2X(1) currents from rundown. We showed that the proximal region of the intracellular C terminus of P2X(1) subunit directly binds to PI(4,5)P(2) and other anionic phospholipids, and we identified the basic residue Lys(364) as a critical determinant for phospholipid binding and sensitivity to wortmannin. Overall, these results indicate that PI(4,5)P(2) plays a key role in the expression of full native and heterologous P2X(1) function by regulating the amplitude, recovery, and kinetics of ionotropic ATP responses through direct receptor-lipid interactions.
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PMID:Direct modulation of P2X1 receptor-channels by the lipid phosphatidylinositol 4,5-bisphosphate. 1852 36