Pharmacological upregulation of h-channels 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.
Division of Neuroscience, Department of Neurology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Nicholas P
NP
Poolos
Michele
M
Migliore
Daniel
D
Johnston
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D000077213:Lamotrigine; D008297:Male; D008959:Models, Neurological; D018408:Patch-Clamp Techniques; D015221:Potassium Channels; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014227:Triazines / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D054815:Cyclic Nucleotide-Gated Cation Channels; D018691:Excitatory Amino Acid Antagonists; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D014227:Triazines; D000077213:Lamotrigine