Acta Physiologica 2008; Volume 194, Supplement 666
Belgian Society for Fundamental and Clinical Physiology and Pharmacology, Spring Meeting 2008
17/05/2008-17/05/2008
University of Liège, Liège, Belgium

SK CHANNEL BLOCKADE PROMOTES BURSTING IN VIVO IN DORSAL RAPHE SEROTONERGIC NEURONS
Abstract number: P-01
Rouchet1 N., Waroux1 O., Alix1 Ph., Scuvee-Moreau1 J., Liegeois2 J-F., Seutin1 V.
1Laboratory of Pharmacology, Center for Cellular and Molecular Neurobiology, 
2Laboratory of Medicinal Chemistry, Natural and Synthetic Drugs Research Center., Univ. Lige, B-4000 Sart Tilman/ Lige 1, Belgium 
SK channels are small conductance calcium-activated potassium channels which trigger an outward current generating a medium-duration afterhyperpolarization (mAHP). This AHP follows a single or a train of action potentials, and therefore is important in the regulation of the firing frequency and/or pattern of many types of neurons. Serotonergic (5-HT) neurons from the raphe nuclei express SK3 channels and exhibit a significant AHP which can be blocked in vitro by apamin and N-methyl laudanosine (NML) (Scuvée-Moreau et al, 2004). In order to further characterize SK currents in 5-HT neurons, patch-clamp recordings were carried out in brain slices. In parallel, we wanted to determine the physiological role of these channels in vivo, by using single unit extracellular recordings combined with iontophoresis of the specific non-peptidic SK channel blocker, UCL1684 (200 mM), in anesthetized rats. In vivo, we observed a significant increase in the production of doublets in 17 out of 25 neurons, with no effect on their mean firing rate as compared to the control condition. The 8 other neurons were completely unaffected. As 5-HT neurons have an important GABAergic input, we applied a GABAA antagonist, SR95531, prior to UCL1684, in order to rule out an indirect effect of the latter. In these conditions, UCL1684 still produced a marked increase of bursting in a subset of 5-HT neurons (11 out of 20).
In voltage-clamp recordings in slices, the mAHP current (peak at ~70 ms) was generated by a depolarizing step from -60 to 100 mV during 20 ms. Application of bicuculline methchloride (BMC), a reversible medium affinity SK channel blocker, or apamin, completely abolished the current. In addition, blockade of the SK current revealed the existence of an inward current which will have to be identified in later experiments.
In conclusion, in vivo, SK channels seem to play a role in controlling the firing pattern of a subgroup of 5-HT neurons. In vitro, the SK current opposes an inward current which could have a role in the bursting behaviour.
To cite this abstract, please use the following information:
Acta Physiologica 2008; Volume 194, Supplement 666 :P-01