The Journal of Neurophysiology Vol. 79 No. 6 June 1998, pp. 2911-2918
Copyright ©1998 The American Physiological Society

Effect of Bicuculline on Thalamic Activity: A Direct Blockade of I_AHP in Reticularis Neurons

Franck Debarbieux², Jennifer Brunton^{1, 2}, and Serge Charpak^{1, 2}

¹ Department of Physiology, University Medical Center, 1211 Geneva 4, Switzerland; and ² Laboratoire de Physiologie, Ecole Supérieure de Physique et Chimie Industrielles de la Ville de Paris, Unité Mixte de Recherche 7637, 75005 Paris, France

Debarbieux, Franck, Jennifer Brunton, and Serge Charpak. Effect of bicuculline on thalamic activity: a direct blockade of I_AHP in reticularis neurons. J. Neurophysiol. 79: 2911-2918, 1998. The thalamic reticular nucleus (RTN) is the major source of inhibitory contacts in the thalamus and thus plays an important role in regulating the excitability of the thalamocortical network. Inhibition occurs through GABAergic synapses on relay cells as well as through GABAergic synapses between reticularis neurons themselves. Here we report that the role and mechanisms of this inhibition, which frequently have been studied using N-methyl derivatives of the -aminobutyric acid-A (GABA_A) receptor antagonist bicuculline, should be revisited. Using the whole cell patch-clamp technique in thalamic slices from young rats, we observed an enhancement by bicuculline methiodide, methobromide, and methochloride (collectively referred to as bicuculline-M; 5-60 µM) of the low-threshold calcium spike burst in RTN neurons that persisted in the presence of tetrodotoxin (1 µM) and was not reproduced in picrotoxin (100-300 µM). The effect did not involve activation of any GABA receptor subtype. Voltage-clamp recordings showed that bicuculline-M blocked the current underlying the low-threshold spike burst afterhyperpolarization (AHP), an effect that was mimicked by apamin (100 nM). Recordings from nucleated patches extracted from reticularis neurons demonstrated that this effect was not mediated by modulation of the release of an unidentified neurotransmitter but that bicuculline-M directly blocks small conductance (SK) channels. The AHP-blocking effect also was observed in other brain regions, demonstrating that although bicuculline-M is a potent GABA_A receptor antagonist, it is of limited value in assessing GABAergic network interactions, which should be studied using picrotoxin or bicuculline-free base. However, bicuculline-M may provide a useful tool for developing nonpeptide antagonists of SK channels.

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