Opposite effects of alpha 1- and beta-adrenoceptor stimulation on both glutamate- and gamma-aminobutyric acid-mediated spontaneous transmission in cultured rat hippocampal neurons.
The effects of adrenergic receptor stimulation on spontaneous synaptic transmission were investigated in cultured rat hippocampal neurons by recording spontaneous excitatory and inhibitory postsynaptic currents (sEPSC and sIPSC). Noradrenaline (NA) inhibited sEPSC in a concentration-dependent manner, with maximal effect at 10 microM. The alpha(1)- and alpha(2)-adrenoceptor-selective agonists cirazoline and clonidine induced an inhibition of sEPSC appearance, whereas the beta-adrenoceptor agonist isoproterenol elicited an increase. The inhibitory effect of NA was reversed by alpha(1)-adrenoceptor blockade. The participation of gamma-aminobutyric acid (GABA)(B)-receptor stimulation in the inhibitory effect of NA was further examined. GABA(B)-receptor stimulation with baclofen induced a strong inhibition of bursting activity, which was fully reversed by the GABA(B) antagonist CGP 55845. By itself, CGP 55845 exerted a stimulatory effect on sEPSC frequency. In the presence of CGP 55845, the inhibitory effects of cirazoline and clonidine were maintained. NA (1, 10, and 100 microM) and alpha-adrenoceptor agonists decreased miniature EPSC and IPSC occurrence, whereas beta-adrenergic stimulation increased it. In 50% of the cells examined, NA (1, 10 microM) had a stimulatory effect on sIPSC, whereas, in the remaining 50% of cells, NA (1, 10 microM) had an inhibitory effect. In all the cells, 100 microM NA induced an inhibition of sIPSC. The inhibitory effect of NA was due to alpha(1)-receptor stimulation, whereas the excitatory effect was due to beta-receptor stimulation. In cultured hippocampal neurons, spontaneous excitatory and inhibitory synaptic transmissions are both similarly altered by adrenoceptor stimulation. However, in a subset of cells, low concentrations of NA mediate an increase of sIPSC via beta-adrenoceptor activation.
Croce
Ariane
A
Laboratoire Plasticité Cérébrale, UMR 5102 CNRS, Université Montpellier II, Montpellier, France.
Astier
Hélène
H
Récasens
Max
M
Vignes
Michel
M
D058646:Adrenergic alpha-1 Receptor Agonists; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D018079:Receptors, GABA / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D058646:Adrenergic alpha-1 Receptor Agonists; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D018079:Receptors, GABA; D017470:Receptors, Glutamate