Voltage-gated Ca2+ channel subtypes mediating GABAergic transmission in the rat supraoptic nucleus.
The supraoptic nucleus receives an abundant gamma-aminobutyric acid (GABA)ergic input which is inhibited by activation of various presynaptic metabotropic receptors. We here analysed the subtypes of voltage-gated Ca2+ channels intervening in the control of transmitter release at these synapses. To address this issue, we tested various specific inhibitors of Ca2+ channels on evoked inhibitory postsynaptic currents (IPSCs). Blocking N- and P-type voltage-gated Ca2+ channels with 1 micromomega-conotoxin-GVIA and 20 nmomega-agatoxin-IVA, respectively, dramatically reduced IPSC amplitude. Q- and L-type Ca2+ channels also contributed to GABAergic transmission, although to a lesser extent, as revealed by applications of 200 nmomega-agatoxin-IVA and of the dihydropyridines nifedipine (10 microm) and nimodipine (10 microm). Evoked IPSCs were insensitive to SNX-482 (300 nm), a blocker of some R-type Ca2+ channels. Analysis of selective blockade by the various antagonists suggested that multiple types of Ca2+ channels synergistically interact to trigger exocytosis at some individual GABA release sites. We next investigated whether inhibition of GABA release in response to the activation of metabotropic glutamate, GABA and adenosine receptors involved the modulation of these presynaptic Ca2+ channels. This was not the case, as the inhibitory actions of selective agonists of these receptors were unaffected by the presence of the different Ca2+ channel antagonists. This finding suggests that these metabotropic receptors modulate GABAergic transmission through a different mechanism, downstream of Ca2+ entry in the terminals, or upstream through the activation of K+ channels.
Bhaukaurally
Khaleel
K
INSERM U.378, Institut François Magendie, 33077 Bordeaux, France.
Panatier
Aude
A
Poulain
Dominique A
DA
Oliet
Stéphane H R
SH
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D020907:Calcium Channels, Q-Type / Q000502:physiology*; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013495:Supraoptic Nucleus / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D020746:Calcium Channels, L-Type; D020907:Calcium Channels, Q-Type; D018755:GABA Agonists; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D000241:Adenosine