Presynaptic and postsynaptic modulation of glutamatergic synaptic transmission by activation of alpha(1)- and beta-adrenoceptors in layer V pyramidal neurons of rat cerebral cortex.
Adrenergic agonists have different modulatory effects on excitatory synaptic transmission depending on the receptor subtypes involved. The present study examined the loci of alpha(1)- and beta-adrenoceptor agonists, which have opposite effects on excitatory neural transmission, involved in modulation of glutamatergic transmission in layer V pyramidal cells of rat cerebral cortex. Phenylephrine, an alpha(1)-adrenoceptor agonist, suppressed the amplitude of AMPA receptor-mediated excitatory postsynaptic currents evoked by repetitive electrical stimulation (eEPSCs, 10 pulses at 33 Hz). The coefficient of variation (CV) of the 1st eEPSC amplitude and paired-pulse ratio (PPR), which were sensitive to extracellular Ca(2+) concentration, were not affected by phenylephrine. Phenylephrine suppressed miniature EPSC (mEPSC) amplitude without changing its frequency. In contrast, isoproterenol, a beta-adrenoceptor agonist, strongly increased the amplitude of the 1st eEPSC compared with that of the 2nd to 10th eEPSCs, which resulted in a decrease in PPR. Isoproterenol-induced enhancement of eEPSC amplitude was accompanied by a decrease in CV. Isoproterenol increased the frequency of mEPSCs without significant effect on amplitude. Phenylephrine suppressed inward currents evoked by puff application of glutamate, AMPA, or NMDA, whereas isoproterenol application was not accompanied by significant changes in these inward currents. These findings suggest that phenylephrine decreases eEPSCs through postsynaptic AMPA or NMDA receptors, while the effects of isoproterenol are mediated by facilitation of glutamate release from presynaptic terminals without effect on postsynaptic glutamate receptors. These two different mechanisms of modulation of excitatory synaptic transmission may improve the "signal-to-noise ratio" in cerebral cortex.
Kobayashi
Masayuki
M
Department of Pharmacology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo 101-8310, Japan. kobayashi-ms@dent.nihon-u.ac.jp
Kojima
Masao
M
Koyanagi
Yuko
Y
Adachi
Kazunori
K
Imamura
Kazuyuki
K
Koshikawa
Noriaki
N
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D018408:Patch-Clamp Techniques / Q000379:methods; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D018663:Adrenergic Agents; D018683:Excitatory Amino Acid Agents; D018756:GABA Antagonists; D011943:Receptors, Adrenergic, beta; D018698:Glutamic Acid; D002118:Calcium; D001640:Bicuculline