Cellular and Molecular Neuroscienceβ-pompilidotoxin modulates spontaneous activity and persistent sodium currents in spinal networks
Research Highlights
▶β-PMTX increases persistent sodium currents (INaP) in spinal neurons. ▶β-PMTX increases intrinsic spiking activity via an up-regulation of INaP. ▶An increase of intrinsic activity suppresses network activity in spinal networks.
Section snippets
Cultures
Cultures were made from the spinal cord of Wistar rats (Janvier, Le Genest St. Isle, France) at embryonic age 14. The cultures were prepared as described previously (Streit et al., 2001). The embryos were delivered by caesarean section from deeply anaesthetized animals (0.4 ml pentobarbital i.m., Streuli Pharma AG, Uznach, Switzerland) and killed by decapitation. Following the delivery of the embryos, the mother was killed by intracardiac injection of pentobarbital. This procedure guarantees a
Results
In the present study, experimental data were obtained from 37 cultures of dissociated spinal cord. From these, 16 were used to study the effect of β-PMTX on network activity with multi site extracellular recordings on MEAs and 21 were investigated with the whole cell patch clamp technique to study sodium currents.
Discussion
In the present study, our experimental results provide three main findings. First, we show that β-PMTX known to act on INaT has an additional effect on INaP. Second, β-PMTX up-regulates the expression of INaP mainly in a specific group of silent spinal cells and turns them into spontaneously spiking interneurons. Third, an enhancement of spontaneously active neurons increases the general intrinsic activity leading to a suppression of the network activity.
Conclusion
In summary, our findings indicate that β-PMTX affects both INaP and the fast inactivation of INaT leading to an increase of the intrinsic activity by switching silent into intrinsically spiking cells and by increasing the firing rate of spiking neurons. At the network level, the consequences are a suppression of the synaptic network activity by the increased intrinsic activity.
Acknowledgments
We thank R. Rubli for doing the culture work and D. de Limoges, H. Ruchti and J. Burkhalter for technical support for the recording setup. We are grateful to H. P. Clamann for critical comments on the manuscript. This work was supported by Swiss National Science Foundation Grants 31-59080.99 and 3100-067048.0
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Present address: CNRS UMR 7224, Physiopathologie des Maladies du Système Nerveux Central, Paris, France INSERM U952, Paris, France UPMC, University Paris 06, Paris, France.