Details

Autor(en) / Beteiligte

• Berger, Thomas
• Lüscher, Hans-R.

Titel

Associative somatodendritic interaction in layer V pyramidal neurons is not affected by the antiepileptic drug lamotrigine

Ist Teil von

• The European journal of neuroscience, 2004-09, Vol.20 (6), p.1688-1693

Ort / Verlag

Oxford, UK: Blackwell Science Ltd

Erscheinungsjahr

2004

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• The antiepileptic drug lamotrigine was described to exert its effects on neuronal excitability via voltage‐gated sodium and calcium, as well as hyperpolarization‐activated conductances. In order to define the effects of lamotrigine on the excitability of layer V pyramidal cells of the rat somatosensory cortex we performed patch‐clamp recordings from the soma and dendrite of this major cortical output cell type in acute slices. Voltage‐clamp experiments revealed the blockade of the persistent sodium current by 50–100 µm lamotrigine as well as by 50 µm of the anticonvulsant drug phenytoin. In somatic current‐clamp studies lamotrigine, in a therapeutic concentration range, depolarizes the membrane potential reflecting the activation of the hyperpolarization‐activated current. This depolarization reduces the rheobase and increases the spiking frequency at the onset of the spike train. For long depolarizing current pulses under lamotrigine, however, a use‐dependent block of sodium channels reduces spiking frequency and spike amplitude. The depolarization due to 50–100 µm lamotrigine reduces additionally the critical frequency of back‐propagating spikes necessary to elicit a dendritic calcium action potential. Ten to thirty micromolar lamotrigine, in contrast, did not change the critical frequency. Lamotrigine blocks long‐lasting, high frequent spiking activity due to its use‐dependent sodium channel block, while burst activity is not impaired due to a depolarizing shift of the membrane potential. This drug therefore dampens epileptic activity while leaving the somatodendritic association in layer V pyramidal cells intact.