Characteristics of AMPA receptor‐mediated responses of cultured cortical and spinal cord neurones and their correlation to the expression of glutamate receptor subunits, GluR1‐4

Abstract

1 Electrophysiological recordings have been used to characterize responses mediated by AMPA receptors expressed by cultured rat cortical and spinal cord neurones. The EC 50 values for AMPA were 17 and 11 mM, respectively. 2 Responses of cortical neurones to AMPA were inhibited competitively by NBQX (pK i =6.6). Lower concentrations of NBQX (41 mM) also potentiated the plateau responses of spinal cord neurones to AMPA, which could be attributed to a depression of desensitization to AMPA. 3 GYKI 52466 inhibited responses of spinal cord neurones to AMPA to about twice the extent of responses of cortical neurones. 4 Blockade of AMPA receptor desensitization by cyclothiazide (CTZ) potentiated responses of spinal cord neurones (6.8 fold) signi®cantly more than responses of cortical neurones (4.8 fold). Responses of cortical neurones to KA were potentiated 3.5 fold by CTZ, while responses of spinal cord neurones were unaected. 5 Ultra-fast applications of AMPA to outside-out patches showed responses of spinal cord neurones desensitized by 97.5% and exhibit marked inward recti®cation, whereas cortical neurones desensitized by 91% and exhibited slight outward recti®cation. The time constants of deactivation and desensitization were about twice as fast in spinal cord than cortical neurones. 6 In cortical neurones, single-cell RT ± PCR showed GluR2 and GluR1 accounted for 91% of all subunits and were expressed together in 67% of neurones, predominantly as the¯ip variants (78%). GluR2 was detected alone in 24% of neurones. GluR3 and GluR4 were present in only 14 and 29% of neurones, respectively. For spinal cord neurones, GluR4 o was detected in 81% of neurones, whereas predominantly¯op versions of GluR1, 2 and 3 were detected in 38, 13 and 13% of neurones, respectively. These expression patterns are related to the respective pharmacological and mechanistic properties.

A corticotropin-releasing factor system expressed in the cochlea modulates hearing sensitivity and protects against noise-induced hearing loss

“…Experiments have demonstrated that GluR4 homomers are functional, and are critical elements of synapses characterized by tonic activity such as those between photoreceptors and bipolar cells of the retina (Pang et al, 2008). Furthermore, spinal cord neurons, in which GluR4 homomers represent at least half of all GluR complexes, reveal a rapid desensitization of AMPA-induced currents compared to cortical neurons that express comparatively little GluR4 (Dai et al, 2001). Because GluR4 homomers are highly desensitizing, spinal cord neurons expressing these receptors flux less current in response to low concentrations of AMPA than cells expressing heteromeric GluRs (Dai et al, 2001).…”

“…Furthermore, spinal cord neurons, in which GluR4 homomers represent at least half of all GluR complexes, reveal a rapid desensitization of AMPA-induced currents compared to cortical neurons that express comparatively little GluR4 (Dai et al, 2001). Because GluR4 homomers are highly desensitizing, spinal cord neurons expressing these receptors flux less current in response to low concentrations of AMPA than cells expressing heteromeric GluRs (Dai et al, 2001). Thus, a switch to a higher proportion of GluR4 homomers in the cochlea may attenuate post-synaptic responses in the face of constant noise-induced glutamate release.…”

AMPA receptor ligands: Synthetic and pharmacological studies of polyamines and polyamine toxins

“…Interestingly, the spinal cord contains only a low level of GluR2 subunits, while they are expressed at higher levels in cultured cortical neurons. 215 This would explain the high sensitivity of non-NMDAR agonist responses to polyamine-containing toxins in spinal neurons. 211 A similar situation arises in NMDAR where receptors containing NR1 subunits in combination with NR2A or NR2B are more sensitive to antagonism by PCCs than those containing NR1 with NR2C or NR2D.…”

Glutamate Receptor-Mediated Oligodendrocyte Toxicity in Periventricular Leukomalacia: A Protective Role for Topiramate

“…Radioactivity of the whole-cell lysate was counted by liquid scintillation. Electrophysiological recordings on pre-OLs were performed using conventional patch-clamp techniques in whole-cell mode as published previously (Dai et al, 2001;Rosenberg et al, 2003). Kainate (100 or 300 M) and topiramate (50 or 100 M; 20 min preincubation) were applied through a gravity perfusion system.…”