Selective modulation of desensitization at AMPA versus kainate receptors by cyclothiazide and concanavalin A

Partin, Kathryn M.; Patneau, D.K.; Winters, Christine A.; Mayer, Mark L.; Buonanno, Andrés

doi:10.1016/0896-6273(93)90220-l

Cited by 558 publications

(469 citation statements)

References 47 publications

Supporting

Mentioning

436

Contrasting

Unclassified

Order By: Relevance

“…11 Hippocampal neurons were treated with kainate (KA) (100 mM) for 5 min, which is not toxic by itself in a short exposure, 17 together with cyclothiazide (CTZ, 30 mM). CTZ is a selective blocker of AMPA receptor desensitization, 19 and is a useful tool to selectively unmask effects mediated by AMPA receptors. 16,17,20 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl] isothiourea (KB-R7943) (20 mM) selectively inhibits the reverse mode of NCX and was used for this purpose, being three-fold more effective on NCX3 than on NCX1 or NCX2.…”

Section: Resultsmentioning

confidence: 99%

Changes in calcium dynamics following the reversal of the sodium-calcium exchanger have a key role in AMPA receptor-mediated neurodegeneration via calpain activation in hippocampal neurons

et al. 2007

View full text Add to dashboard Cite

Proteolytic cleavage of the Na þ /Ca 2 þ exchanger (NCX) by calpains impairs calcium homeostasis, leading to a delayed calcium overload and excitotoxic cell death. However, it is not known whether reversal of the exchanger contributes to activate calpains and trigger neuronal death. We investigated the role of the reversal of the NCX in Ca 2 þ dynamics, calpain activation and cell viability, in a-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-stimulated hippocampal neurons. The sodium-calcium exchanger (NCX) plays a fundamental role in controlling Na þ and Ca 2 þ homeostasis. 1,2 NCX primarily extrudes Ca 2 þ in exchange for Na þ , whereas upon neuronal depolarization, Na þ is pumped out by NCX, while Ca 2 þ is pumped in. In pathophysiological conditions, overactivation of glutamate receptors can cause the reversal of NCX, leading to Ca 2 þ entry into the cell. 3 Three NCX genes have been identified, NCX1, 4 NCX2 5 and NCX3. 6 In excitotoxic cell death, an increase in intracellular free calcium concentration ([Ca 2 þ ] i ) may directly cause activation of Ca 2 þ -dependent cysteine proteases, the calpains. Calpains modulate a variety of physiological processes, 7 and are important mediators of cell death. 8,9 Calpains mediate the neurotoxic effect of N-methyl-D-aspartate (NMDA) in cultured hippocampal neurons by a caspase-independent cell death mechanism of excitotoxicity. 10 Calpains are also involved in the neurotoxic effect caused by a-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor activation in cultured hippocampal neurons, 11 and in hippocampal slice cultures. 12 During excitotoxic neurodegeneration, calpains are responsible for the proteolysis of several cytoskeletal and associated proteins, kinases and phosphatases, membrane receptors and transporters. 13 Recently, the involvement of calpains in the cleavage of NCX was described in cultured cerebellar granule neurons exposed to glutamate and following brain ischemia. 14 The NCX3 subtype is inactivated by proteolytic cleavage by calpains, and is no longer able to pump Ca 2 þ out of the cell, thus enhancing cell death. Furthermore, NCX3 was shown to be more relevant for cell survival than NCX1 or NCX2, namely in cultured cerebellar granule neurons. 14, 15 We recently reported that neurotoxicity induced by activation of AMPA receptors is characterized by calpain activation, lack of caspase activation, nuclear condensation/fragmentation, release of cytochrome c from mitochondria, decreased intracellular ATP levels, production of nitric oxide, moderate superoxide production and increased levels of peroxynitrite. [16][17][18] In this in vitro model of excitotoxicity, the cell

show abstract

Section: Resultsmentioning

confidence: 99%

Changes in calcium dynamics following the reversal of the sodium-calcium exchanger have a key role in AMPA receptor-mediated neurodegeneration via calpain activation in hippocampal neurons

et al. 2007

View full text Add to dashboard Cite

show abstract

“…This Ca ++ influx triggers a cascade of secondary messengers which ultimately activate a number of enzymes such as protein kinase C (PKC), phospholipase A2 (PLA2), phospholipase C (PLC), Ca ++ -calmodulindependent protein kinase II (CaM kinase II), and others [272][273][274][275][276][277][278] . Consequently, these processes lead to fixation of changes in postsynaptic AMPA receptors such as an increase in their affinity and number [279][280][281][282][283] , and possibly through retrograde signals from arachidonic acid and nitric oxide 284 , modulate presynaptic glutamatergic terminals influencing [285][286][287][288][289][290] .…”

Section: ) Synaptic Plasticitymentioning

confidence: 99%

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Rousseaux

2008

J Toxicol Pathol

View full text Add to dashboard Cite

Seventy years ago it was discovered that glutamate is abundant in the brain and that it plays a central role in brain metabolism. However, it took the scientific community a long time to realize that glutamate also acts as a neurotransmitter. Glutamate is an amino acid and brain tissue contains as much as 5 -15 mM glutamate per kg depending on the region, which is more than of any other amino acid. The main motivation for the ongoing research on glutamate is due to the role of glutamate in the signal transduction in the nervous systems of apparently all complex living organisms, including man. Glutamate is considered to be the major mediator of excitatory signals in the mammalian central nervous system and is involved in most aspects of normal brain function including cognition, memory and learning. In this review, the basic biology of the excitatory amino acids glutamate, glutamate receptors, GABA, and glycine will first be explored. In the second part of this review, the known pathophysiology and pathology will be described. (J Toxicol Pathol 2008; 21: 25-51)

show abstract

“…These developmental effects are mediated directly and indirectly by the same classes ofreceptors that are used for excitatory communication and the generation of plasticity in the adult brain, namely, AMPA/low-affinity kainate (AMPA-preferring), high-affinity kainate (kainate-preferring), NMDA-gated channels and metabotropic receptors (reviewed by Young and Fagg, 1990;Monaghan and Anderson, 1991;Gasic and Hollmann, 1992;Nakanishi, 1992;Monaghan, 1993;Wisden and Seeburg 1993a,b). Kainate-preferring receptors can be constructed from subunits GluR-5, GluR-6, GluR-7, KA-1, and KA-2/y2 (Bettler et al, 1990(Bettler et al, , 1992Egebjerg et al, 1991;Werner et al, 1991;Herb et al, 1992;Lomeli et al, 1992;Sakimura et al, 1992;Sommer et al, 1992;Partin et al, 1993;Wenthold et al, 1993;reviewed Wisden and Seeburg, 1993a,b). They can be generated in vitro from recombinant homomeric (GluR-5 and GluR-6) or heteromeric configurations (e.g., KA-2/GluR-6), and form channels with rapidly desensitizing responses to kainate (Herb et al, 1992;Sakimura et al, 1992;Sommer et al, 1992), and can further be distinguished from AMPA receptors because their desensitization rate can be modulated by ConA but not cyclothiozide (Partin et al, 1993).…”

mentioning

confidence: 99%

“…Kainate-preferring receptors can be constructed from subunits GluR-5, GluR-6, GluR-7, KA-1, and KA-2/y2 (Bettler et al, 1990(Bettler et al, , 1992Egebjerg et al, 1991;Werner et al, 1991;Herb et al, 1992;Lomeli et al, 1992;Sakimura et al, 1992;Sommer et al, 1992;Partin et al, 1993;Wenthold et al, 1993;reviewed Wisden and Seeburg, 1993a,b). They can be generated in vitro from recombinant homomeric (GluR-5 and GluR-6) or heteromeric configurations (e.g., KA-2/GluR-6), and form channels with rapidly desensitizing responses to kainate (Herb et al, 1992;Sakimura et al, 1992;Sommer et al, 1992), and can further be distinguished from AMPA receptors because their desensitization rate can be modulated by ConA but not cyclothiozide (Partin et al, 1993). These kainate-gated channels are probably physiologically modulatable at the synapse by CAMP dependent phosphorylation (Raymond et al, 1993;Wang et al, 1993).…”

mentioning

confidence: 99%

Kainate receptor gene expression in the developing rat brain

1994

View full text Add to dashboard Cite

Kainate-preferring receptors are a subclass of ionotropic glutamate receptors that might play a role in brain development. The expression of the five known genes encoding kainate receptor subunits (GluR-5, -6, -7, KA-1, and KA-2) was studied by in situ hybridization during pre- and postnatal development of the rat brain. We compared the combined expression patterns of these genes with autoradiography using 3H- kainate in the developing brain from embryonic day 12 (E12) through to adult. Although mRNAs for the receptor subunits (except KA-1) can be detected at stage E12, 3H-kainic acid binding (as an index of receptor protein) is not found at this stage. However, by E14 high-affinity kainate sites are found throughout the gray matter, but particularly in spinal cord, primordial cerebellum, and ventral forebrain structures. All genes undergo a peak in their expression in the late embryonic/early postnatal period. GluR-5 expression during development shows the most interesting features because the changes are qualitative. The GluR-5 gene shows peaks of expression around the period of birth in the sensory cortex (layers II, III, and IV), in CA1 hippocampal interneurons in the stratum oriens, in the septum, and in the thalamus. GluR-6 shows a prenatal expression peak in the cingulate gyrus of the neocortex. KA-1 transcripts appear with the development of the hippocampus and remain largely confined to discrete areas such as the CA3 region, the dentate gyrus, and subiculum. KA-2 transcripts are found throughout the CNS from as early as E12 and remain constant until adulthood. The GluR-5 and GluR-6 genes are coexpressed in multiple peripheral ganglia (e.g., cranial nerve ganglia, dorsal root ganglia, and mural ganglia) at E14.

show abstract

Selective modulation of desensitization at AMPA versus kainate receptors by cyclothiazide and concanavalin A

Cited by 558 publications

References 47 publications

Changes in calcium dynamics following the reversal of the sodium-calcium exchanger have a key role in AMPA receptor-mediated neurodegeneration via calpain activation in hippocampal neurons

Changes in calcium dynamics following the reversal of the sodium-calcium exchanger have a key role in AMPA receptor-mediated neurodegeneration via calpain activation in hippocampal neurons

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Kainate receptor gene expression in the developing rat brain

Contact Info

Product

Resources

About