An apamin-sensitive Ca2+-activated K+ current in hippocampal pyramidal neurons

Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4662-7. doi: 10.1073/pnas.96.8.4662.

Abstract

In hippocampal and other cortical neurons, action potentials are followed by afterhyperpolarizations (AHPs) generated by the activation of small-conductance Ca2+-activated K+ channels (SK channels). By shaping the neuronal firing pattern, these AHPs contribute to the regulation of excitability and to the encoding function of neurons. Here we report that CA1 pyramidal neurons express an AHP current that is suppressed by apamin and is involved in the control of repetitive firing. This current presents distinct kinetic and pharmacological features, and it is modulated differently than the apamin-insensitive slow AHP current. Furthermore, our in situ hybridizations show that the apamin-sensitive SK subunits are expressed in CA1 pyramidal neurons, providing a potential molecular correlate to the apamin-sensitive AHP current. Altogether, these results clarify the discrepancy between the reported high density of apamin-binding sites in the CA1 region and the apparent lack of an apamin-sensitive current in CA1 pyramidal neurons, and they may explain the effects of this toxin on hippocampal synaptic plasticity and learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apamin / pharmacology*
  • Base Sequence
  • Bicuculline / pharmacology
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / pharmacology
  • Hippocampus / physiology*
  • In Situ Hybridization
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides / chemistry
  • Oligodeoxyribonucleotides, Antisense / chemistry
  • Potassium Channels / drug effects
  • Potassium Channels / genetics
  • Potassium Channels / physiology*
  • Potassium Channels, Voltage-Gated*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology*
  • Rats
  • Thionucleotides / pharmacology

Substances

  • Oligodeoxyribonucleotides
  • Oligodeoxyribonucleotides, Antisense
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Thionucleotides
  • potassium channel protein I(sk)
  • Apamin
  • 8-((4-chlorophenyl)thio)cyclic-3',5'-AMP
  • Cyclic AMP
  • Bicuculline