Associative somatodendritic interaction in layer V pyramidal neurons is not affected by the antiepileptic drug lamotrigine |
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Authors: | Berger Thomas Lüscher Hans-R |
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Institution: | Institute of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland. berger@pyl.unibe.ch |
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Abstract: | 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 micro m lamotrigine as well as by 50 micro m 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 micro m 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. |
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Keywords: | cortex dendrite hyperpolarization‐activated cationic current neuronal integration rat somatosensory sodium current |
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