Hippocalcin gates the calcium activation of the slow afterhyperpolarization in hippocampal pyramidal cells

Neuron. 2007 Feb 15;53(4):487-93. doi: 10.1016/j.neuron.2007.01.011.


In the brain, calcium influx following a train of action potentials activates potassium channels that mediate a slow afterhyperpolarization current (I(sAHP)). The key steps between calcium influx and potassium channel activation remain unknown. Here we report that the key intermediate between calcium and the sAHP channels is the diffusible calcium sensor hippocalcin. Brief depolarizations sufficient to activate the I(sAHP) in wild-type mice do not elicit the I(sAHP) in hippocalcin knockout mice. Introduction of hippocalcin in cultured hippocampal neurons leads to a pronounced I(sAHP), while neurons expressing a hippocalcin mutant lacking N-terminal myristoylation exhibit a small I(sAHP) that is similar to that recorded in uninfected neurons. This implies that hippocalcin must bind to the plasma membrane to mediate its effects. These findings support a model in which the calcium sensor for the sAHP channels is not preassociated with the channel complex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Calcium / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Egtazic Acid / pharmacology
  • Electric Stimulation / methods
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Hippocalcin / deficiency
  • Hippocalcin / physiology*
  • Hippocampus / cytology*
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / genetics*
  • Ion Channel Gating / radiation effects
  • Membrane Potentials / drug effects
  • Membrane Potentials / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation / physiology
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology*
  • Pyramidal Cells / radiation effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Small-Conductance Calcium-Activated Potassium Channels / physiology*
  • Transfection / methods


  • Cell Cycle Proteins
  • G2A receptor
  • Potassium Channel Blockers
  • Receptors, G-Protein-Coupled
  • Small-Conductance Calcium-Activated Potassium Channels
  • Green Fluorescent Proteins
  • Hippocalcin
  • Egtazic Acid
  • Calcium