KCNQ/M channels control spike afterdepolarization and burst generation in hippocampal neurons

J Neurosci. 2004 May 12;24(19):4614-24. doi: 10.1523/JNEUROSCI.0765-04.2004.


KCNQ channel subunits are widely expressed in peripheral and central neurons, where they give rise to a muscarinic-sensitive, subthreshold, and noninactivating K+ current (M-current). It is generally agreed that activation of KCNQ/M channels contributes to spike frequency adaptation during sustained depolarizations but is too slow to influence the repolarization of solitary spikes. This concept, however, is based mainly on experiments with muscarinic agonists, the multiple effects on membrane conductances of which may overshadow the distinctive effects of KCNQ/M channel block. Here, we have used selective modulators of KCNQ/M channels to investigate their role in spike electrogenesis in CA1 pyramidal cells. Solitary spikes were evoked by brief depolarizing current pulses injected into the neurons. The KCNQ/M channel blockers linopirdine and XE991 markedly enhanced the spike afterdepolarization (ADP) and, in most neurons, converted solitary ("simple") spikes to high-frequency bursts of three to seven spikes ("complex" spikes). Conversely, the KCNQ/M channel opener retigabine reduced the spike ADP and induced regular firing in bursting neurons. Selective block of BK or SK channels had no effect on the spike ADP or firing mode in these neurons. We conclude that KCNQ/M channels activate during the spike ADP and limit its duration, thereby precluding its escalation to a burst. Consequently, down-modulation of KCNQ/M channels converts the neuronal firing pattern from simple to complex spiking, whereas up-modulation of these channels exerts the opposite effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Anthracenes / pharmacology
  • Carbamates / pharmacology
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Indoles / pharmacology
  • Neurons / drug effects
  • Neurons / physiology*
  • Phenylenediamines / pharmacology
  • Potassium / metabolism
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology
  • Pyridines / pharmacology
  • Rats


  • 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone
  • Anthracenes
  • Carbamates
  • Indoles
  • Phenylenediamines
  • Potassium Channel Blockers
  • Potassium Channels
  • Pyridines
  • ezogabine
  • linopirdine
  • Potassium