Modulation of K+ current by frequency and external [K+]: a tale of two inactivation mechanisms

Neuron. 1995 Oct;15(4):951-60. doi: 10.1016/0896-6273(95)90185-x.


Voltage-activated K+ currents and their inactivation properties are important for controlling frequency-dependent signaling in neurons and other excitable cells. Two distinct molecular mechanisms for K+ channel inactivation have been described: N-type, which involves rapid occlusion of the open channel by an intracellular tethered blocker, and C-type, which involves a slower change at the extracellular mouth of the pore. We find that frequency-dependent cumulative inactivation of Shaker channels is very sensitive to changes of extracellular [K+] in the physiological range, with much more inactivation at low [K+]out, and that it results from the interaction of N- and C-type inactivation. N-type inactivation enhances C-type inactivation by two mechanisms. First, it inhibits outward K+ flux, which normally fills an external ion site and thus prevents C-type inactivation. Second, it keeps the channel's activation gate open even after repolarization, allowing C-type inactivation to occur for a prolonged period.

Publication types

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

MeSH terms

  • Cell Line
  • Electric Conductivity
  • Embryo, Mammalian
  • Gene Deletion
  • Humans
  • Ion Channel Gating / drug effects
  • Kidney
  • Kinetics
  • Mutation
  • Potassium / metabolism
  • Potassium / pharmacology*
  • Potassium Channels / drug effects*
  • Potassium Channels / genetics
  • Potassium Channels / physiology*
  • Transfection


  • Potassium Channels
  • Potassium