Modulation of HCN channels in lateral septum by nicotine

Neuropharmacology. 2014 Jun:81:274-82. doi: 10.1016/j.neuropharm.2014.02.012. Epub 2014 Feb 26.

Abstract

The effects of addictive drugs most commonly occur via interactions with target receptors. The same is true of nicotine and its multiple receptors in a variety of cell types. However, there are also side effects for given substances that can dramatically change cellular, tissue, organ, and organism functions. In this study, we present evidence that nicotine possesses such properties, and modulates neuronal excitability. We recorded whole-cell voltages and currents in neurons situated in the dorsal portion of the lateral septum in acute coronal brain slices of adult rats. Our experiments in the lateral septum revealed that nicotine directly affects HCN - hyperpolarization-activated cyclic nucleotide gated non-selective cation channels. We demonstrate that nicotine effects persist despite the concurrent application of nicotinic acetylcholine receptors' antagonists - mecamylamine, methyllycaconitine, and dihydro-β-erythroidine. These results are novel in regard to HCN channels in the septum, in general, and in their sensitivity to nicotine, in particular.

Keywords: Action potentials; HCN channels; Sag potential; Septal neurons; h-Current.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / drug effects*
  • Animals
  • Biophysical Phenomena / drug effects
  • Biophysics
  • Cyclic Nucleotide-Gated Cation Channels / metabolism*
  • Dihydro-beta-Erythroidine / pharmacology
  • Electric Stimulation
  • In Vitro Techniques
  • Mecamylamine / pharmacology
  • Neurons / drug effects*
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology*
  • Nicotinic Antagonists / pharmacology
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Septal Nuclei / cytology*
  • Septal Nuclei / drug effects

Substances

  • Cyclic Nucleotide-Gated Cation Channels
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Dihydro-beta-Erythroidine
  • Mecamylamine
  • Nicotine