Selective activation of Ca2+-activated K+ channels by co-localized Ca2+ channels in hippocampal neurons

Nature. 1998 Oct 29;395(6705):900-5. doi: 10.1038/27674.


Calcium entry through voltage-gated calcium channels can activate either large- (BK) or small- (SK) conductance calcium-activated potassium channels. In hippocampal neurons, activation of BK channels underlies the falling phase of an action potential and generation of the fast afterhyperpolarization (AHP). In contrast, SK channel activation underlies generation of the slow AHP after a burst of action potentials. The source of calcium for BK channel activation is unknown, but the slow AHP is blocked by dihydropyridine antagonists, indicating that L-type calcium channels provide the calcium for activation of SK channels. It is not understood how this specialized coupling between calcium and potassium channels is achieved. Here we study channel activity in cell-attached patches from hippocampal neurons and report a unique specificity of coupling. L-type channels activate SK channels only, without activating BK channels present in the same patch. The delay between the opening of L-type channels and SK channels indicates that these channels are 50-150 nm apart. In contrast, N-type calcium channels activate BK channels only, with opening of the two channel types being nearly coincident. This temporal association indicates that N and BK channels are very close. Finally, P/Q-type calcium channels do not couple to either SK or BK channels. These data indicate an absolute segregation of coupling between channels, and illustrate the functional importance of submembrane calcium microdomains.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium / metabolism*
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Electrophysiology
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • In Vitro Techniques
  • Ion Channel Gating
  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Potassium Channels, Calcium-Activated*
  • Pyramidal Cells / metabolism*
  • Small-Conductance Calcium-Activated Potassium Channels


  • Calcium Channels
  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Small-Conductance Calcium-Activated Potassium Channels
  • Egtazic Acid
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium