Associative somatodendritic interaction in layer V pyramidal neurons is not affected by the antiepileptic drug lamotrigine.
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.
Berger
Thomas
T
Institute of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland. berger@pyl.unibe.ch
Lüscher
Hans-R
HR
D000200:Action Potentials / Q000187:drug effects / Q000528:radiation effects; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology*; D003712:Dendrites / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D066298:In Vitro Techniques; D000077213:Lamotrigine; D018408:Patch-Clamp Techniques / Q000379:methods; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects; D013003:Somatosensory Cortex / Q000166:cytology*; D014227:Triazines / Q000494:pharmacology*
D000927:Anticonvulsants; D015222:Sodium Channels; D014227:Triazines; D000077213:Lamotrigine