Effects of ZD7288 on firing pattern of thermosensitive neurons isolated from hypothalamus

Neurosci Lett. 2012 Jan 11;506(2):336-41. doi: 10.1016/j.neulet.2011.11.041. Epub 2011 Dec 2.

Abstract

The role of the hyperpolarization-activated current (Ih) mediated by HCN channels in temperature sensing by the hypothalamus was addressed. In warm-sensitive neurons (WSNs), exposure to ZD7288, an inhibitor of Ih mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, decreased their action potential amplitudes and frequencies significantly. By contrast, ZD7288 had little or no effect on temperature-insensitive neurons (TINs). Exposure of WSNs to ZD7288 led to a significant increase in the duration of the inter-spike interval and a reduction of Ih irreversibly. These results suggest that ZD7288 have the contrasting effects on the firing patterns of WSNs versus TINs, which implies HCN channels play a central role in temperature sensing by hypothalamic neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Body Temperature Regulation / drug effects
  • Body Temperature Regulation / physiology*
  • Cardiotonic Agents / pharmacology*
  • Cyclic Nucleotide-Gated Cation Channels / drug effects
  • Cyclic Nucleotide-Gated Cation Channels / metabolism
  • Hypothalamus / drug effects
  • Hypothalamus / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Cardiotonic Agents
  • Cyclic Nucleotide-Gated Cation Channels
  • Pyrimidines
  • ICI D2788