title: Adrenergic regulation of GABA release from presynaptic terminals in rat cerebral cortex.
abstract: The α1-adrenoceptor agonist phenylephrine and the β-adrenoceptor agonist isoproterenol have opposite effects on evoked EPSPs (eEPSPs) in the cerebral cortex. The suppressive effects of phenylephrine on eEPSPs are mediated by modulation of postsynaptic glutamate receptors, whereas enhancement of eEPSPs by isoproterenol is due to facilitation of glutamate release from presynaptic terminals. The present study used whole-cell patch-clamp recordings from layer V pyramidal neurons in visuocortical slice preparations to assess the effects of phenylephrine and isoproterenol on the release probability of γ-aminobutyric acid (GABA). The present study recorded evoked inhibitory postsynaptic potentials (eIPSCs) by repetitive electrical stimulation (duration, 100 μs; 10 stimuli at 33 Hz) and miniature IPSCs (mIPSCs). The effects of phenylephrine (100 μM) depended on the amplitude of eIPSCs: phenylephrine decreased the paired-pulse ratios (PPRs) of eIPSCs with smaller amplitudes (<~600 pA) but increased PPRs of eIPSCs with larger amplitude. Phenylephrine also exhibited amplitude-dependent modulation of mIPSCs, i.e., an increase in the frequency of smaller mIPSC events (<~20 pA) and a decrease in the frequency of larger events. These findings suggest that α1-adrenoceptor activation facilitates GABA release from a subpopulation of GABAergic terminals that induce smaller-amplitude IPSCs in postsynaptic neurons. In contrast, isoproterenol (100 μM) consistently decreased the PPR of eIPSCs and increased the frequency of mIPSCs, suggesting that presynaptic β-adrenoceptors increase release probability from most GABAergic terminals. The complexity of adrenoceptor modulations in GABAergic synaptic transmission by α1-adrenoceptor and β-adrenoceptor activation may be due to the presence of pleiotropic subtypes of GABAergic interneurons in the cerebral cortex.
authors.affiliation: Department of Pharmacology, Nihon University School of Dentistry.
authors.forename: Masanori
authors.initials: M
authors.lastname: Terakado
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D008297:Male; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid