Noradrenergic enhancement of GABA-induced input resistance changes in layer V regular spiking pyramidal neurons of rat somatosensory cortex

Brain Res. 1995 Mar 27;675(1-2):171-82. doi: 10.1016/0006-8993(95)00060-4.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Animals
  • Colforsin / pharmacology
  • Electrophysiology
  • In Vitro Techniques
  • Isoproterenol / pharmacology
  • Membrane Potentials / drug effects
  • Microelectrodes
  • Muscimol / pharmacology
  • Norepinephrine / pharmacology*
  • Pyramidal Cells / drug effects*
  • Rats
  • Somatosensory Cortex / cytology
  • Somatosensory Cortex / drug effects*
  • gamma-Aminobutyric Acid / pharmacology*


  • Colforsin
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Muscimol
  • gamma-Aminobutyric Acid
  • Isoproterenol
  • Norepinephrine