Noradrenaline mediates paradoxical effects on rat neocortical neurons after GABA withdrawal.
1. The aim of the present study was to determine the role of noradrenergic neurotransmission in neuronal activities intracellularly recorded in neocortical slices obtained from rats presenting the gamma-aminobutyric acid (GABA) withdrawal syndrome (GWS), a focal epilepsy consecutive to the interruption of a chronic intracortical GABA infusion into the somatomotor cortex. Neurons recorded in the epileptic focus area (n = 52) were bursting or nonbursting cells. Intrinsic bursting (IB, n = 20) cells presented bursts of action potentials (APs) to an intracellular depolarizing current injection and paroxysmal depolarization shifts (PDSs) to white matter stimulation. Synaptic bursting (SB, n = 22) cells presented only PDSs. Nonbursting (NB, n = 10) cells presented no burst after either synaptic stimulation or depolarizing current injection. Results were compared with those obtained from NB neurons (n = 4) recorded in slices from saline-infused rats. 2. In all of the recorded neurons, bath application of norepinephrine (NE, 10 and 100 microM) provoked a depolarization (1-5 mV) associated with a decrease in input K+ conductance having a mean reversal potential at -90 to -102 mV, not significantly different for bursting and nonbursting cells. This reversal potential differed from that of Cl(-)-mediated inhibitory postsynaptic potentials (-70 mV) elicited in NB cells by electrical stimulation of the white matter. 3. In IB cells, the NE-induced depolarization replaced the intrinsic bursts by a sustained repetitive discharge of single APs and caused intrinsic bursts to appear during previously subthreshold depolarizing current pulses. These NE-increased activities were abolished by dihydropyridine nitrendipine (1 microM) and by Cd2+ (0.5 mM) or Co2+ (2 mM), thus confirming that Ca2+ currents contribute to burst generation in IB cells. 4. In both NB and SB cells recorded in slices from GWS rats, NE provoked the appearance of intrinsic bursts of APs during steps of depolarizing current injections. In addition, in NB cells, NE caused synaptic bursts to appear after white matter stimulation. These NE-induced bursts were dihydropyridine (nitrendipine, 1 microM)- and Cd2+ (0.5 mM)- or Co2+ (2 mM)-sensitive and were related to an increased AP-afterdepolarization. The fast AP-afterhyperpolarization was not affected by NE. In NB cells recorded in slices from saline-infused rats (n = 4) NE did not provoke the appearance of bursts even when stimulation intensity was increased up to three times.(ABSTRACT TRUNCATED AT 400 WORDS)
Silva-Barrat
C
C
Institut Alfred Fessard, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
Champagnat
J
J
Leiva
J
J
Pavlik
V
V
D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D002540:Cerebral Cortex / Q000503:physiopathology*; D046508:Culture Techniques; D004195:Disease Models, Animal; D004828:Epilepsies, Partial / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009044:Motor Cortex / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013003:Somatosensory Cortex / Q000503:physiopathology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D015220:Calcium Channels; D015221:Potassium Channels; D005680:gamma-Aminobutyric Acid; D009638:Norepinephrine