Abstract
In the developing visual cortex, the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit GluR4 precedes that of the other AMPAR subunits GluR1-3, and then declines to become almost absent in adults. The current study shows that the neuronal activity regulates the expression of GluR4 by a culture system in vitro and a dark-rearing (DR) system in vivo. Membrane depolarization by treatment of cultured neurons of the visual cortex with a high concentration of KCl (35 mm; HK) promoted a decline in the expression of GluR4. This effect of HK on the expression of GluR4 was significantly blocked by the addition of an N-methyl-d-aspartate receptor (NMDAR) antagonist, (D)-2-amino-5-phosphonovaleric acid (APV), but not by the voltage-sensitive calcium channel antagonist nifedipine. Moreover, the Ca(2+)-calmodulin-dependent kinase (CaMKII) inhibitor KN62 and the cAMP-dependent protein kinase A (PKA) inhibitor H-89 blocked this effect, which suggests the involvement of Ca(2+) influx via NMDAR and the subsequent activation of CaMKII and PKA. Conversely, the MAP kinase inhibitor PD98059 promoted the effect of HK on the expression of GluR4. Significantly, APV, KN62, H-89 and PD98059 either promoted or inhibited the expression of GluR4 even in normal KCl (5 mm) conditions. The developmental change in the expression of GluR4 was significantly attenuated in DR in vivo, and the results suggest that neuronal activity such as visual experience may be involved in the mechanism of the expression of GluR4, which is mediated by NMDAR and tuned by certain protein kinases at an early developmental stage in the visual cortex.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.