Activation of a metabotropic excitatory amino acid receptor potentiates spike-driven calcium increases in neurons of the dorsolateral septum.
(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), an agonist for metabotropic glutamate receptors (mGluRs), causes depolarization and burst firing in rat dorsolateral septal nucleus (DLSN) neurons and results in long-term potentiation (LTP) at DLSN synapses. In the present study, we investigated whether these actions of 1S,3R-ACPD are attributable to the release of calcium from an inositol triphosphate-sensitive store after activation of mGluRs coupled to phospholipase C. Our data demonstrated that the ACPD-induced depolarization was associated with a small but significant decrease, not an increase, in [Ca2+]i; however, changes of [Ca2+]i, during ACPD-induced bursting were up to seven times larger than those produced by regular firing. Depletion of internal calcium stores by thapsigargin or ryanodine had a small to insignificant effect on the maximum changes of [Ca2+]i, associated with ACPD-induced bursting. Thus, elevation of [Ca2+]i, during firing by 1S,3R-ACPD is likely attributable to enhancement of calcium influx through voltage-gated channels and not to calcium release from internal stores. ACPD-induced burst firing elevated somatic and dendritic calcium levels up to 3 and 6 microM, respectively. Such an increase may be the underlying mechanism for ACPD-induced LTP as well as ACPD-induced acute cell death in rat DLSN.
Zheng
F
F
Roche Institute of Molecular Biology, Nutley, New Jersey 07110-1199, USA.
Gallagher
J P
JP
Connor
J A
JA
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D003712:Dendrites / Q000378:metabolism; D005456:Fluorescent Dyes; D016257:Fura-2; D006706:Homeostasis; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000502:physiology*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012688:Septum Pellucidum / Q000166:cytology / Q000378:metabolism* / Q000502:physiology
D005456:Fluorescent Dyes; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D002118:Calcium; D016257:Fura-2