PMID- 18684909
OWN - NLM
STAT- MEDLINE
DCOM- 20090420
LR  - 20171116
IS  - 0022-3077 (Print)
IS  - 0022-3077 (Linking)
VI  - 100
IP  - 5
DP  - 2008 Nov
TI  - SK (KCa2) channels do not control somatic excitability in CA1 pyramidal neurons 
      but can be activated by dendritic excitatory synapses and regulate their impact.
PG  - 2589-604
LID - 10.1152/jn.90433.2008 [doi]
AB  - Calcium-activated K(+) channels of the K(Ca)2 type (SK channels) are prominently 
      expressed in the mammalian brain, including hippocampus. These channels are 
      thought to underlie neuronal excitability control and have been implicated in 
      plasticity, memory, and neural disease. Contrary to previous reports, we found 
      that somatic spike-evoked medium afterhyperpolarizations (mAHPs) and 
      corresponding excitability control were not caused by SK channels but mainly by 
      Kv7/KCNQ/M channels in CA1 hippocampal pyramidal neurons. Thus apparently, these 
      SK channels are hardly activated by somatic Na(+) spikes. To further test this 
      conclusion, we used sharp electrode, whole cell, and perforated-patch recordings 
      from rat CA1 pyramidal neurons. We found that SK channel blockers consistently 
      failed to suppress mAHPs under a range of experimental conditions: mAHPs 
      following single spikes or spike trains, at -60 or -80 mV, at 20-30 degrees C, in 
      low or elevated extracellular [K(+)], or spike trains triggered by synaptic 
      stimulation after blocking N-methyl-d-aspartic acid receptors (NMDARs). 
      Nevertheless, we found that SK channels in these cells were readily activated by 
      artificially enhanced Ca(2+) spikes, and an SK channel opener 
      (1-ethyl-2-benzimidazolinone) enhanced somatic AHPs following Na(+) spikes, thus 
      reducing excitability. In contrast to CA1 pyramidal cells, bursting pyramidal 
      cells in the subiculum showed a Na(+) spike-evoked mAHP that was reduced by 
      apamin, indicating cell-type-dependent differences in mAHP mechanisms. Testing 
      for other SK channel functions in CA1, we found that field excitatory 
      postsynaptic potentials mediated by NMDARs were enhanced by apamin, supporting 
      the idea that dendritic SK channels are activated by NMDAR-dependent calcium 
      influx. We conclude that SK channels in rat CA1 pyramidal cells can be activated 
      by NMDAR-mediated synaptic input and cause feedback regulation of synaptic 
      efficacy but are normally not appreciably activated by somatic Na(+) spikes in 
      this cell type.
FAU - Gu, Ning
AU  - Gu N
AD  - Dept. of Physiology at IMB and Centre for Molecular Biology and Neuroscience 
      (CMBN), University of Oslo., PB 1103 Blindern, N-0317 Oslo, Norway.
FAU - Hu, Hua
AU  - Hu H
FAU - Vervaeke, Koen
AU  - Vervaeke K
FAU - Storm, Johan F
AU  - Storm JF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080806
PL  - United States
TA  - J Neurophysiol
JT  - Journal of neurophysiology
JID - 0375404
RN  - 0 (10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone)
RN  - 0 (Anthracenes)
RN  - 0 (Benzimidazoles)
RN  - 0 (Calcium Channel Agonists)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Small-Conductance Calcium-Activated Potassium Channels)
RN  - 24345-16-2 (Apamin)
RN  - 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione)
RN  - M82W79SS4W (1-ethyl-2-benzimidazolinone)
SB  - IM
MH  - 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology
MH  - Animals
MH  - Anthracenes/pharmacology
MH  - Apamin/pharmacology
MH  - Benzimidazoles/pharmacology
MH  - Calcium Channel Agonists/pharmacology
MH  - Dendrites/drug effects/*physiology
MH  - Drug Interactions
MH  - Electric Stimulation/methods
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Excitatory Postsynaptic Potentials/drug effects/physiology/radiation effects
MH  - Hippocampus/*cytology
MH  - In Vitro Techniques
MH  - Male
MH  - Patch-Clamp Techniques/methods
MH  - Potassium Channel Blockers/pharmacology
MH  - Pyramidal Cells/*cytology/*physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Small-Conductance Calcium-Activated Potassium Channels/*physiology
MH  - Synapses/drug effects/*physiology
EDAT- 2008/08/08 09:00
MHDA- 2009/04/21 09:00
CRDT- 2008/08/08 09:00
PHST- 2008/08/08 09:00 [pubmed]
PHST- 2009/04/21 09:00 [medline]
PHST- 2008/08/08 09:00 [entrez]
AID - 90433.2008 [pii]
AID - 10.1152/jn.90433.2008 [doi]
PST - ppublish
SO  - J Neurophysiol. 2008 Nov;100(5):2589-604. doi: 10.1152/jn.90433.2008. Epub 2008 
      Aug 6.