Proceedings of The Physiological Society

University of Leeds (2002) J Physiol 544P, S014


Population of neurones within dorsal and dorsomedial regions of the nucleus of the solitary tract that are sensitive to 4-AP and TEA

Mark L. Dallas, Susan A. Deuchars, David I. Lewis and Jim Deuchars

School of Biomedical Sciences, University of Leeds, Leeds LS2 9NQ, UK

The Kv3 subfamily of Kv channels consists of four genes (Kv3.1-3.4) and each Kv3 gene encodes multiple products by alternative splicing. Kv3.1 and Kv3.2 channels have been located within distinct populations of central neurones, with these channels endowing repetitive firing properties on neurones (for review, see Rudy et al. 1999). We have previously shown the existence of Kv3.1b subunits of these channels in specific neurones within the nucleus of the solitary tract by immunoreactivity (NTS, Deuchars & Atkinson, 2001). The aim of the present study was to examine the role of the Kv3.1 channels in determining the firing properties of NTS neurones. Male Wistar rats (15-21 days) were terminally anaesthetized with sodium pentobarbitone (120 mg kg-1, I.P.) and humanely killed by decapitation. 300 mm coronal slices of the medulla oblongata were prepared. Whole-cell patch-clamp recordings were made from 50 NTS neurones from dorsal and dorsomedial regions of this nucleus and their firing properties were examined pre- and post-application of 4-AP (30 mM) and TEA (0.5 mM). At these specific concentrations if similar effects are observed then it is likely to be due to action on the Kv3.1 subunit (Coetzee et al. 1999). In 38 neurones 4-AP increased the action potential (AP) duration from 4.5 ± 1.5 to 10.3 ± 3.7 ms (mean ± S.D., P < 0.05, Student's paired t test), decreased the AHP amplitude from 17.4 ± 3.2 to 10.4 ± 2.9 mV (P < 0.05) and the steady-state firing frequency from 12.7 ± 0.9 to 8.7 ± 1.8 Hz (P < 0.05). TEA was tested in 25 of these 38 and seen to increase the AP duration from 5.1 ± 1.3 to 12.5 ± 4.2 ms (P < 0.05), and decrease the AHP amplitude from 18.6 ± 2.3 to 14.1 ± 4.1 mV (P < 0.05) and the steady-state firing frequency from 13.4 ± 1.3 to 7.5 ± 1.4 Hz (P < 0.05). Twelve neurones were insensitive to the application of the pharmacological agents. Two neurones were sensitive to TEA and insensitive to 4-AP. These data indicate that a subset of NTS neurones are sensitive to low concentrations of 4-AP and TEA, and are suggestive of a role for Kv3.1 channels in the neuronal output of specific neurones within dorsal and dorsomedial regions of the NTS. Ongoing studies are looking at the phenotype of these neurones and the circuits they are involved in.

This study was supported by the University of Leeds.

All procedures accord with current UK legislation.

Where applicable, experiments conform with Society ethical requirements