Characterization of the K + channel opening effect of the anticonvulsant retigabine in PC12 cells

Characterization of the K + channel opening effect of the anticonvulsant retigabine in PC12 cells Retigabine (D-23129) is a new anticonvulsant compound which acts as a K + channel opener in neuronal cells. The aim of the present study was to further characterize the retigabine induced K + current. In nerve growth factor treated PC12 cells and in rat cortical neurones the application of retigabine activated a K + current. In contrast, however, no K + current activation was observed in untreated PC12 and in glial cells which were cultivated together with the neuronal cells. To characterise the retigabine activated K + current, K + channel blockers were used. The retigabine induced current was not affected by 1 and 10 mM 4-aminopyridine (4AP). Ba 2+ 1 mM resulted in a reduction of 88.6±3.0% ( n =5); 10 mM abolished the current. Tetraetylamonium (TEA), 1 and 10 mM, reduced the current by 23.6±3.1 and 61.6±3.7%, respectively. To investigate the current/voltage ( I / V ) relation of the current initiated by retigabine (10 μM), cells were clamped to a holding potential of −80 mV and a ramp stimulation protocol (−120 to +60 mV in 5 s) was applied prior to and during application of retigabine. Subtraction of the two traces yielded the current induced by retigabine. A nearly linear relationship was determined between −120 and −40 mV. At potentials positive to −40 mV, the response was variable. This was due to the additionally observed weak blocking effect of retigabine on delayed rectifier ( K dr ) currents. If the ramp was applied in the presence of 10 mM 4AP to block K dr , a nearly linear I / V -relationship was present from −120 to +60 mV. The comparison of the I / V relation and pharmacology with published K + channel subtypes gives evidence that an unknown neuronal K + channel subtype may be involved. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Epilepsy Research Elsevier

Characterization of the K + channel opening effect of the anticonvulsant retigabine in PC12 cells

Epilepsy Research, Volume 35 (2) – Jun 1, 1999

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Publisher
Elsevier
Copyright
Copyright © 1999 Elsevier Science B.V.
ISSN
0920-1211
D.O.I.
10.1016/S0920-1211(98)00131-4
Publisher site
See Article on Publisher Site

Abstract

Retigabine (D-23129) is a new anticonvulsant compound which acts as a K + channel opener in neuronal cells. The aim of the present study was to further characterize the retigabine induced K + current. In nerve growth factor treated PC12 cells and in rat cortical neurones the application of retigabine activated a K + current. In contrast, however, no K + current activation was observed in untreated PC12 and in glial cells which were cultivated together with the neuronal cells. To characterise the retigabine activated K + current, K + channel blockers were used. The retigabine induced current was not affected by 1 and 10 mM 4-aminopyridine (4AP). Ba 2+ 1 mM resulted in a reduction of 88.6±3.0% ( n =5); 10 mM abolished the current. Tetraetylamonium (TEA), 1 and 10 mM, reduced the current by 23.6±3.1 and 61.6±3.7%, respectively. To investigate the current/voltage ( I / V ) relation of the current initiated by retigabine (10 μM), cells were clamped to a holding potential of −80 mV and a ramp stimulation protocol (−120 to +60 mV in 5 s) was applied prior to and during application of retigabine. Subtraction of the two traces yielded the current induced by retigabine. A nearly linear relationship was determined between −120 and −40 mV. At potentials positive to −40 mV, the response was variable. This was due to the additionally observed weak blocking effect of retigabine on delayed rectifier ( K dr ) currents. If the ramp was applied in the presence of 10 mM 4AP to block K dr , a nearly linear I / V -relationship was present from −120 to +60 mV. The comparison of the I / V relation and pharmacology with published K + channel subtypes gives evidence that an unknown neuronal K + channel subtype may be involved.

Journal

Epilepsy ResearchElsevier

Published: Jun 1, 1999

References

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