Pharmacological upregulation of h-channels selectively reduces the excitability of pyramidal neuron dendrites

The dendrites of pyramidal neurons have markedly different electrical
properties from those of the soma, owing to the non-uniform distribution
of voltage-gated ion channels in dendrites. It is thus possible that drugs
acting on ion channels might preferentially alter dendritic, but not
somatic, excitability. Using dendritic and somatic whole-cell and cell-
attached recordings in rat hippocampal slices, we found that the
anticonvulsant lamotrigine selectively reduced action potential firing
from dendritic depolarization, while minimally affecting firing at the
soma. This regional and input-specific effect resulted from an increase in
the hyperpolarization-activated cation current (I(h)), a voltage-gated
current present predominantly in dendrites. These results demonstrate that
neuronal excitability can be altered by drugs acting selectively on
dendrites, and suggest an important role for I(h) in controlling dendritic
excitability and epileptogenesis.