Noradrenergic enhancement of GABA-induced input resistance changes in layer V regular spiking pyramidal neurons of rat somatosensory cortex.
Previous in vivo studies have shown that microiontophoretic application of norepinephrine (NE) and isoproterenol (ISO) can enhance gamma-aminobutyric acid (GABA)-induced depressant responses of rat somatosensory cortical neurons. In the present investigation we have examined the transmembrane electrophysiological events which are associated with interactions between NE and GABA in layer V pyramidal neurons of rat barrel field cortex. Intracellular recordings were made from electrophysiologically identified cells in a superfused cortical tissue slice preparation before, during and after bath or microdrop application of GABA, NE and ISO, alone or in combination. GABA application produced a small depolarization from resting membrane potential associated with a reduction (22%) in input resistance. NE and ISO (10-100 microM) also produced in some cases small membrane depolarizations (1-4 mV) but little concomitant changes in input resistance. Simultaneous application of NE with GABA potentiated amino acid-induced changes in input resistance in 4 cases and antagonized (n = 4) or had no effect (n = 4) on GABA-associated membrane events in 8 other cases. When the alpha-blocker, phentolamine (20 microM), was added to the medium, NE-induced enhancement of the GABA response was observed in 3 of 5 cases (60%), suggesting both, a beta-adrenergic mediation and a possible alpha-receptor masking of this noradrenergic-potentiating action. Consistent with this interpretation was the finding that the beta-agonist, ISO (10-100 microM), produced net increases in GABA-induced input resistance changes in 64% of cases tested (9 of 14). The potentiating effect of NE and ISO was mimicked by the adenyl cyclase activator, forskolin (n = 2), and a membrane permeant analog of cyclic-AMP, 8-bromo-cyclic AMP (n = 3); and could also be demonstrated when the GABAA agonist muscimol (0.5-1 microM) was substituted for GABA. The reversal potential for GABA and GABA + NE remained the same. These findings suggest that previous demonstrations of NE-potentiating effects on GABA inhibition may be mediated by beta-receptor/cyclic-AMP-linked actions on mechanisms which regulate GABAA receptor-induced membrane conductance changes.
Sessler
F M
FM
Department of Anatomy and Neurobiology, Medical College of Pennsylvania, Philadelphia 19102, USA.
Liu
W
W
Kirifides
M L
ML
Mouradian
R D
RD
Lin
R C
RC
Waterhouse
B D
BD
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009118:Muscimol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D013003:Somatosensory Cortex / Q000166:cytology / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D007545:Isoproterenol; D009638:Norepinephrine