Channelpedia

PubMed 24719109


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ2 , KCNQ3 , KCNQ5 , Kv7.2 , Kv7.3 , Kv7.5



Title: Conditional deletions of epilepsy-associated KCNQ2 and KCNQ3 channels from cerebral cortex cause differential effects on neuronal excitability.

Authors: Heun Soh, Rima Pant, Joseph J LoTurco, Anastasios V Tzingounis

Journal, date & volume: J. Neurosci., 2014 Apr 9 , 34, 5311-21

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24719109


Abstract
KCNQ2 and KCNQ3 potassium channels have emerged as central regulators of pyramidal neuron excitability and spiking behavior. However, despite an abundance of evidence demonstrating that KCNQ2/3 heteromers underlie critical potassium conductances, it is unknown whether KCNQ2, KCNQ3, or both are obligatory for maintaining normal pyramidal neuron excitability. Here, we demonstrate that conditional deletion of Kcnq2 from cerebral cortical pyramidal neurons in mice results in abnormal electrocorticogram activity and early death, whereas similar deletion of Kcnq3 does not. At the cellular level, Kcnq2-null, but not Kcnq3-null, CA1 pyramidal neurons show increased excitability manifested as a decreased medium afterhyperpolarization and a longer-lasting afterdepolarization. As a result, these Kcnq2-deficient neurons are hyperexcitable, responding to current injections with an increased number and frequency of action potentials. Biochemically, the Kcnq2 deficiency secondarily results in a substantial loss of KCNQ3 and KCNQ5 protein levels, whereas loss of Kcnq3 only leads to a modest reduction of other KCNQ channels. Consistent with this finding, KCNQ allosteric activators can still markedly dampen neuronal excitability in Kcnq3-null pyramidal neurons, but have only weak effects in Kcnq2-null pyramidal neurons. Together, our data reveal the indispensable function of KCNQ2 channels at both the cellular and systems levels, and demonstrate that pyramidal neurons have near normal excitability in the absence of KCNQ3 channels.