Cyclic ADP ribose-dependent Ca2+ release by group I metabotropic glutamate receptors in acutely dissociated rat hippocampal neurons.
Group I metabotropic glutamate receptors (group I mGluRs; mGluR1 and mGluR5) exert diverse effects on neuronal and synaptic functions, many of which are regulated by intracellular Ca(2+). In this study, we characterized the cellular mechanisms underlying Ca(2+) mobilization induced by (RS)-3,5-dihydroxyphenylglycine (DHPG; a specific group I mGluR agonist) in the somata of acutely dissociated rat hippocampal neurons using microfluorometry. We found that DHPG activates mGluR5 to mobilize intracellular Ca(2+) from ryanodine-sensitive stores via cyclic adenosine diphosphate ribose (cADPR), while the PLC/IP(3) signaling pathway was not involved in Ca(2+) mobilization. The application of glutamate, which depolarized the membrane potential by 28.5±4.9 mV (n = 4), led to transient Ca(2+) mobilization by mGluR5 and Ca(2+) influx through L-type Ca(2+) channels. We found no evidence that mGluR5-mediated Ca(2+) release and Ca(2+) influx through L-type Ca(2+) channels interact to generate supralinear Ca(2+) transients. Our study provides novel insights into the mechanisms of intracellular Ca(2+) mobilization by mGluR5 in the somata of hippocampal neurons.
Department of Physiology and Biomembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul, Korea.
Jong-Woo
JW
Sohn
Weon-Jin
WJ
Yu
Doyun
D
Lee
Hee-Sup
HS
Shin
Suk-Ho
SH
Lee
Won-Kyung
WK
Ho
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D036563:Cyclic ADP-Ribose / Q000378:metabolism*; D016257:Fura-2 / Q000031:analogs & derivatives / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018091:Receptors, AMPA / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D020746:Calcium Channels, L-Type; C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; D019837:Ryanodine Receptor Calcium Release Channel; C104077:metabotropic glutamate receptor type 1; C049925:fura-2-am; D036563:Cyclic ADP-Ribose; D012433:Ryanodine; D018698:Glutamic Acid; D002118:Calcium; D016257:Fura-2