Involvement of hippocampal CA3 K(ATP) channels in contextual memory

Neuropharmacology. 2009 Mar;56(3):615-25. doi: 10.1016/j.neuropharm.2008.11.001. Epub 2008 Nov 25.


This paper evaluates the involvement of hippocampal ATP-sensitive potassium channels (K(ATP)) in learning and memory. After confirming expression of the Kir6.2 subunit in the CA3 region of C57BL/6J mice, we performed intra-hippocampal pharmacological injections of specific openers and blockers of K(ATP) channels. The opener diazoxide, the blocker tolbutamide, or a mixture of both, were bilaterally injected in the CA3 region before we subjected the animals to a fear conditioning paradigm. Diazoxide strongly impaired contextual memory of mice at both doses tested. This impairment was specifically reversed by co-injecting the blocker tolbutamide. Moreover, we studied the mnemonic abilities of mice deleted for the Kir6.2 subunit. These mice were backcrossed to C57BL/6J mice and tested in two learning paradigms. We found a significant impairment of contextual and tone memories in the Kir6.2 knock-out mice when compared with heterozygous or wild-type animals. Furthermore, these animals were also slightly impaired in a spatial version of the Morris water maze task. Our data suggest a specific involvement of hippocampal K(ATP) Kir6.2/SUR1 channels in memory processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diazoxide / pharmacology
  • Fear
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • KATP Channels / agonists*
  • KATP Channels / antagonists & inhibitors*
  • Locomotion
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Potassium Channels, Inwardly Rectifying / genetics
  • Tolbutamide / pharmacology


  • KATP Channels
  • Kir6.2 channel
  • Potassium Channels, Inwardly Rectifying
  • Tolbutamide
  • Diazoxide