Activation of Kainate Receptors on Rat Sensory Neurons Evokes Action Potential Firing and May Modulate Transmitter Release

Lee, C. Justin; Engelman, Holly S.; MacCDERMOTT, A. B.

doi:10.1111/j.1749-6632.1999.tb11325.x

Cited by 20 publications

(21 citation statements)

References 8 publications

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“…A number of studies (Cossart et al, 1998;Frerking et al, 1998;RodriguezMoreno et al, 2000;Schmitz et al, 2000) have demonstrated depolarization and repetitive firing of action potentials by hippocampal interneurons after activation of postsynaptic kainate receptors by kainate or ATPA. In addition, Lee et al (1999) observed that 100 M kainate was sufficient to cause some action potential firing in DRG neurons. The dose of kainate (10 M) used to affect DRG 3 spinal transmission in our study, however, did not induce somatic depolarization or action potential firing in Figure 6.…”

Section: Presynaptic Kainate Receptor-mediated Regulation Of Transmitmentioning

confidence: 99%

“…Defining a physiological role for these receptors has remained elusive, however, in part because of the slow development of selective agonists and antagonists. The observations that kainate receptor activation selectively depressed evoked C-fiber volleys (Agrawal and Evans, 1986) and caused action potential firing in cultured DRG cells (Lee et al, 1999) raised the possibility that, by depolarizing presynaptic fibers, kainate receptor agonists might regulate transmitter release at primary afferent synapses. In this study, we report that activation of presynaptic kainate receptors reduces glutamate release from DRG neurons onto their dorsal horn targets.…”

Section: Abstract: Kainate Presynaptic Atpa Glutamate Receptor Sumentioning

confidence: 99%

“…Because we used superfusion with exogenous kainate receptor agonists to achieve modulation of presynaptic glutamate release in our experiments, it is difficult to be certain where on presynaptic cells the relevant kainate receptors are located. It has been proposed that kainate receptors are preferentially distributed to the central terminals of DRG neurons, on which they would be poised to act as true autoreceptors (Agrawal and Evans, 1986;Lee et al, 1999). Previous work (Agrawal and Evans, 1986) has demonstrated particularly strong physiological responses when kainate was applied to centrally projecting axons between the ganglia and the cord.…”

Section: Presynaptic Kainate Receptor-mediated Regulation Of Transmitmentioning

confidence: 99%

“…A potential link between axonal depolarization and suppression of glutamate release has been proposed by Ozawa (1998, 2000), who demonstrated reduced action potential-triggered Ca 2ϩ influx into mossy fiber terminals with presynaptic kainate receptor activation. In the spinal cord, Lee et al (1999) showed that kainate application increased the frequency of spontaneous, tetrodotoxin-insensitive postsynaptic currents, although the synapses responsible for these currents (excitatory vs inhibitory; primary afferent synapses vs local synapses) were not identified. Although we do not provide direct evidence that presynaptic kainate receptor activation suppresses primary afferent transmission by depolarization of presynaptic fibers, our data are at least consistent with such a model.…”

Section: Presynaptic Kainate Receptor-mediated Regulation Of Transmitmentioning

confidence: 99%

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Presynaptic Kainate Receptors Regulate Spinal Sensory Transmission

Kerchner¹,

Wilding

Li³

et al. 2001

J. Neurosci.

142

112

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Small diameter dorsal root ganglion (DRG) neurons, which include cells that transmit nociceptive information into the spinal cord, are known to express functional kainate receptors. It is well established that exposure to kainate will depolarize C-fiber afferents arising from these cells. Although the role of kainate receptors on sensory afferents is unknown, it has been hypothesized that presynaptic kainate receptors may regulate glutamate release in the spinal cord. Here we show that kainate, applied at low micromolar concentrations in the presence of the AMPA-selective antagonist (RS)-4-(4-aminophenyl)-1,2-dihydro-1-methyl-2-propyl-carbamoyl-6,7-methylenedioxyphthalazine, suppressed spontaneous NMDA receptor-mediated EPSCs in cultures of spinal dorsal horn neurons. In addition, kainate suppressed EPSCs in dorsal horn neurons evoked by stimulation of synaptically coupled DRG cells in DRG-dorsal horn neuron cocultures. Interestingly, although the glutamate receptor subunit 5-selective kainate receptor agonist (RS)-2-␣-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA) (2 M) was able to suppress DRG-dorsal horn synaptic transmission to a similar extent as kainate (10 M), it had no effect on excitatory transmission between dorsal horn neurons. Agonist applications revealed a striking difference between kainate receptors expressed by DRG and dorsal horn neurons. Whereas DRG cell kainate receptors were sensitive to both kainate and ATPA, most dorsal horn neurons responded only to kainate. Finally, in recordings from dorsal horn neurons in spinal slices, kainate and ATPA were able to suppress NMDA and AMPA receptormediated EPSCs evoked by dorsal root fiber stimulation. Together, these data suggest that kainate receptor agonists, acting at a presynaptic locus, can reduce glutamate release from primary afferent sensory synapses. Key words: kainate, presynaptic, ATPA, glutamate receptor subunit 5, glutamate, autoreceptor, excitatory synaptic transmission, NMDAGlutamate is the major excitatory transmitter at primary afferent synapses, at which it conveys sensory information to the CNS via postsynaptic AMPA, NMDA, and kainate (KA) receptors on spinal cord dorsal horn neurons (Yoshimura and Jessell, 1990;Li et al., 1999). In addition to postsynaptic receptors, many neurons express on their presynaptic terminals ionotropic receptors that are thought to regulate transmitter release , including receptors for heterologous transmitters as well as autoreceptors for the transmitter(s) released by the terminal itself.Much recent effort has focused on kainate receptors as possible presynaptic regulators of transmission. In the hippocampus, for example, presynaptic kainate receptor activation appears to reduce release of both glutamate (Chittajallu et al., 1996;Kamiya and Ozawa, 1998) and GABA (Clarke et al., 1997; RodriguezMoreno et al., 1997) (but see Frerking et al., 1999). At primary afferent synapses in the spinal cord, in addition to the postsynaptic kainate receptors that contribute to EPSCs evoked by highth...

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Section: Presynaptic Kainate Receptor-mediated Regulation Of Transmitmentioning

confidence: 99%

Section: Abstract: Kainate Presynaptic Atpa Glutamate Receptor Sumentioning

confidence: 99%

Section: Presynaptic Kainate Receptor-mediated Regulation Of Transmitmentioning

confidence: 99%

Section: Presynaptic Kainate Receptor-mediated Regulation Of Transmitmentioning

confidence: 99%

See 2 more Smart Citations

Presynaptic Kainate Receptors Regulate Spinal Sensory Transmission

Kerchner¹,

Wilding

Li³

et al. 2001

J. Neurosci.

142

112

View full text Add to dashboard Cite

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“…For example, PGE2 can induce sensitization of the cell body in vitro (Baccaglini & Hogan, 1983;Fowler, Wonderlin, & Weinreich, 1985;Gold, Dastmalchi, & Levine, 1996;Nicol & Cui, 1994;Vasko, Campbell, & Waite, 1994;Weinreich & Wonderlin, 1987). Furthermore, the sensory neuron cell body in vitro can be induced to release neurotransmitters (Gu, Albuquerque, Lee, & MacDermott, 1996;Gu & MacDermott, 1997;Lee, Engelman, & MacDermott, 1999;MacDermott, Role, & Siegelbaum, 1999), which is Ca 2+ -dependent (Huang et al, 1996).…”

Section: Insert Figure 4 About Here ---------------------------------mentioning

confidence: 99%

The biopsychosocial approach to chronic pain: Scientific advances and future directions.

Gatchel¹,

Peng²,

Peters³

et al. 2007

Psychological Bulletin

2,589

1,903

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The prevalence and cost of chronic pain is a major physical and mental health care problem in the United States today. As a result, there has been a recent explosion of research on chronic pain, with significant advances in better understanding its etiology, assessment and treatment. The purpose of the present article is to provide a review of the most noteworthy developments in the field. The biopsychosocial model is now widely accepted as the most heuristic approach to chronic pain. With this model in mind, a review of the basic neuroscience processes of pain (the bio part of biopsychosocial), as well as the psychosocial factors is presented. This spans research on how psychological and social factors can interact with brain processes to influence health and illness, to the development of new technologies, such as brain imaging, that provide new insights into brain-pain mechanisms.KEY WORDS: biopsychosocial; chronic pain; neuroscience of pain; pain and cognition; pain and emotion Biopsychosocial Approach to Chronic Pain 3The Biopsychosocial Approach to Chronic Pain: Scientific Advances and Future Directions During the past decade, there has been an explosion of research on chronic pain, with significant advances in understanding its etiology, assessment and treatment (Gatchel, 2004; Turk & Monarch, 2002). This research has important health care implications Epidemiological research has shown that chronic pain (loosely defined as prolonged and persistant pain of at least 3-months duration) and chronic recurrent pain (recurrent episodes of pain interspersed with pain free periods extending over months or years) affects 10% -20% of adults in the general population (Blyth et al., 2001; Gureje, Von Korff, Simon & Gater, 1998; Vehaak, Kerssens, Dekker, Sorbi & Bensing, 1998). For example, in a large-scale epidemiological study, Von Korff, Crane, Lane et al. (2005) estimated a 19% prevalence for chronic spinal pain (neck and back) in the U.S. in the previous year, and a 29% lifetime rate. The American Academy of Pain Management (2003) asserted that approximately 57% of all adult Americans reported experiencing recurrent or chronic pain in the past year. About 62% of those individuals reporting being in pain for more than 1 year, and 40% noted that they were constantly in pain. Indeed, as Gatchel (2004) has summarized that pain is a pervasive medical problem: it affects over 50 million Americans and costs more than $70 billion annually in health care costs and lost productivity; it accounts for more than 80% of all physician visits. Moreover, chronic pain is often associated with major comorbid psychiatric disorders and emotional suffering.As the above factors attest, the prevalence and cost of chronic pain is a major physical and mental health care problem in the United States. Moreover, individuals 50 years of age and older are twice as likely to have been diagnosed with chronic pain (Gatchel, 2004;. Currently, there are approximately 35 million Americans aged 65 years or older, accounting for 12.4% of t...

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Presynaptic kainate receptors in primary afferents to the superficial laminae of the rat spinal cord

Hwang

Pagliardini

Rustioni

et al. 2001

J of Comparative Neurology

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Subunits of glutamate receptors participate in the regulation of sensory transmission at primary afferent synapses in the superficial laminae of dorsal horn (DH). We report here on the distribution of kainate receptors (GluR5/6/7) in these laminae by using light microscope (LM) and electron microscope (EM) immunocytochemistry. Standard (4%) paraformaldehyde fixation resulted in immunostaining for GluR5/6/7 in perikarya and fine processes in lamina II, especially its inner part (IIi). Preembedding EM revealed immunostaining of dendrites, perikarya, and occasional terminals, presumed to be from primary afferent fibers, at the center of glomerular arrangements. In rats perfused with 0.5% paraformaldehyde, LM showed a more punctate staining, mainly in the ventral part of lamina IIi and lamina III, than in material fixed with 4% paraformaldehyde. Approximately two-thirds of GluR5/6/7 puncta were also immunostained with synaptophysin, suggesting that in material fixed with 0.5% paraformaldehyde, a large fraction of these are synaptic terminals. Double immunostained puncta disappear 4 days after dorsal rhizotomy, suggesting that most of GluR5/6/7-immunopositive terminals are from primary afferent fibers. EM material fixed with 0.5% paraformaldehyde confirmed the expression of GluR5/6/7 in numerous synaptic endings with morphology of primary afferents. To determine the type of primary afferent terminals that express GluR5/6/7, two neuroanatomic tracers were injected in the sciatic nerves. The lectin from Bandeiraea simplicifolia (IB4) is selectively taken up by unmyelinated primary afferent fibers that terminate in the outer part of lamina II (IIo) and dorsal part of lamina IIi, whereas the B subunit of the cholera toxin (CTB) is selectively taken up by a broader class of primary afferents which, in superficial DH, terminate mainly in laminae I, ventral part of IIi, and III. Approximately 20% of GluR5/6/7-immunoreactive puncta colocalized with IB4, whereas approximately 40% of GluR5/6/7-immunoreactive puncta colocalized with CTB. The present study shows that (1) GluR5/6/7 does not have a clear and consistent spatial relation with postsynaptic sites, (2) a large number of primary afferents express GluR5/6/7, and (3) these are not limited to one functional class. Thus, modulation by glutamate of primary afferent terminals by means of kainate receptors in the superficial laminae of DH may predominantly involve presynaptic mechanisms.

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Activation of Kainate Receptors on Rat Sensory Neurons Evokes Action Potential Firing and May Modulate Transmitter Release

Cited by 20 publications

References 8 publications

Presynaptic Kainate Receptors Regulate Spinal Sensory Transmission

Presynaptic Kainate Receptors Regulate Spinal Sensory Transmission

The biopsychosocial approach to chronic pain: Scientific advances and future directions.

Presynaptic kainate receptors in primary afferents to the superficial laminae of the rat spinal cord

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