Group III metabotropic glutamate receptor agonists modulate high voltage-activated Ca2+ currents in pyramidal neurons of the adult rat.
In pyramidal neurons of the rat sensorimotor cortex, we have investigated the modulation of high voltage-activated calcium currents by agonists at group III metabotropic glutamate receptors (mGluRs). l-2-Amino-4-phosphonobutyrate (l-AP4) and l-serine-O-phosphate (l-SOP) reduced calcium currents in the vast majority of cells isolated from the adult animal. Interestingly, this modulation was negligible in the young animals (2-14 postnatal days), becoming prominent only after full development (more than 21 days). The efficacy of l-SOP mimicked l-AP4 in reducing calcium currents. Yet, l-SOP produced saturating responses at about 3 microM and significant modulation at nanomolar concentrations (EC50=923 nM). The voltage-dependence of the group III mGluR-mediated responses was evaluated by comparing the inhibition of "standard" and "facilitated" conductances. On the calcium currents facilitated by depolarizing prepulse, 3 microM l-SOP produced a mean 13.4% inhibition compared with 19.6% in control condition, supporting the proposition that part of the inodulation was voltage-dependent. The calcium current inhibition caused by the activation of group III metabotropic glutamate receptors was only partially sensitive to omega-conotoxin GVIA, but largely inhibited by omega-agatoxin IVA, at concentrations (100 nM) known to block P- and Q-type channels. Conversely, the dihydropyridine antagonists nifedipine and nimodipine (50-500 nM) failed to prevent the group III mGluR-mediated response in the majority of tested cells (more than 65%). Furthermore, the long-lasting tail promoted by the inclusion of the dihydropyridine agonist Bay K 8644 was not consistently affected by l-SOP and l-AP4. These findings imply that the observed modulation involves different channel subtypes, namely N- and P- or Q-type channels, and suggests that group III mGluRs play an important role in the intrinsic and synaptic functions of adult cortical pyramidal neurons.
Stefani
A
A
Clinica Neurologica, Dip. Sanità Pubblica, Università di Roma Tor Vergata, Italy. stefani@utovrm.it
Spadoni
F
F
Bernardi
G
G
D000375:Aging / Q000502:physiology; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects; D004553:Electric Conductivity; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D008297:Male; D010768:Phosphoserine / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*
D000613:Aminobutyrates; D015220:Calcium Channels; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; D010768:Phosphoserine; C012729:2-amino-4-phosphonobutyric acid; D002118:Calcium