A1 adenosine receptor-mediated GIRK channels contribute to the resting conductance of CA1 neurons in the dorsal hippocampus

J Neurophysiol. 2015 Apr 1;113(7):2511-23. doi: 10.1152/jn.00951.2014. Epub 2015 Feb 4.


The dorsal and ventral hippocampi are functionally and anatomically distinct. Recently, we reported that dorsal Cornu Ammonis area 1 (CA1) neurons have a more hyperpolarized resting membrane potential and a lower input resistance and fire fewer action potentials for a given current injection than ventral CA1 neurons. Differences in the hyperpolarization-activated cyclic nucleotide-gated cation conductance between dorsal and ventral neurons have been reported, but these differences cannot fully account for the different resting properties of these neurons. Here, we show that coupling of A1 adenosine receptors (A1ARs) to G-protein-coupled inwardly rectifying potassium (GIRK) conductance contributes to the intrinsic membrane properties of dorsal CA1 neurons but not ventral CA1 neurons. The block of GIRKs with either barium or the more specific blocker Tertiapin-Q revealed that there is more resting GIRK conductance in dorsal CA1 neurons compared with ventral CA1 neurons. We found that the higher resting GIRK conductance in dorsal CA1 neurons was mediated by tonic A1AR activation. These results demonstrate that the different resting membrane properties between dorsal and ventral CA1 neurons are due, in part, to higher A1AR-mediated GIRK activity in dorsal CA1 neurons.

Keywords: A1 adenosine receptors; GIRK; dorsal and ventral hippocampus.

Publication types

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

MeSH terms

  • Adenosine A1 Receptor Antagonists / pharmacology
  • Animals
  • Barium / pharmacology
  • Bee Venoms / pharmacology
  • CA1 Region, Hippocampal / physiology*
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / antagonists & inhibitors
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / physiology*
  • Male
  • Membrane Potentials* / drug effects
  • Potassium Channel Blockers / pharmacology
  • Pyramidal Cells / physiology*
  • Rats, Sprague-Dawley
  • Receptor, Adenosine A1 / physiology*
  • Xanthines / pharmacology


  • Adenosine A1 Receptor Antagonists
  • Bee Venoms
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Potassium Channel Blockers
  • Receptor, Adenosine A1
  • Xanthines
  • Barium
  • tertiapin
  • 1,3-dipropyl-8-cyclopentylxanthine