Metabotropic glutamate receptor modulation of glutamate responses in the suprachiasmatic nucleus

Authors
Citation
Ll. Haak, Metabotropic glutamate receptor modulation of glutamate responses in the suprachiasmatic nucleus, J NEUROPHYS, 81(3), 1999, pp. 1308-1317
Citations number
102
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROPHYSIOLOGY
ISSN journal
00223077 → ACNP
Volume
81
Issue
3
Year of publication
1999
Pages
1308 - 1317
Database
ISI
SICI code
0022-3077(199903)81:3<1308:MGRMOG>2.0.ZU;2-0
Abstract
Glutamate is the primary excitatory transmitter in the suprachiasmatic nucl eus (SCN). Ionotropic glutamate receptors (iGluRs) mediate transduction of light information from the retina to the SCN, an important circadian clock phase shifting pathway. Metabotropic glutamate receptors (mGluRs) may play a significant modulatory role. mGluR modulation of SCN responses to glutama te was investigated with fura-2 calcium imaging in SCN exp]ant cultures. SC N neurons showed reproducible calcium responses to glutamate, kainate, and N-methyl-D-aspartate (NMDA). Although the type I/II mGluR agonists L-CCG-I and t-ACPD did not evoke calcium responses, they did inhibit kainate- and N MDA-evoked calcium rises. This interaction was insensitive to pertussis tox in Protein kinase A (PKA) activation by 8-bromo-cAMP significantly reduced iGluR inhibition by mGluR agonists. The inhibitory effect of mGluRs was enh anced by activating protein kinase C (PKC) and significantly reduced in the presence of the PKC inhibitor H7. Previous reports show that L-type calciu m channels can be modulated by PKC and PKA. In SCN cells, about one-half of the calcium rise evoked by kainate or NMDA was blocked by the L-type calci um channel antagonist nimodipine. Calcium rises evoked by K+ were used to t est whether mGluR inhibition of iGluR calcium rises involved calcium channe l modulation. These calcium rises were primarily attributable to activation of voltage-activated calcium channels. PKC activation inhibited K+-evoked calcium rises, but PKC inhibition did nest affect L-CCG-I inhibition of the se rises. In contrast, 8Br-cAMP had no effect alone but blocked L-CCG-I inh ibition. Taken together, these results suggest that activation of mGluRs, l ikely type II, modulates glutamate-evoked calcium responses in SCN neurons. mGluR inhibition of iGluR calcium rises can be differentially influenced b y PKC or PKA activation. Regulation of glutamate-mediated calcium influx co uld occur at L-type calcium channels, K+ channels, or at GluRs. it is propo sed that mGluRs may he important regulators of glutamate: responsivity in t he circadian system.