Key result
Pten haploinsufficiency decreases cortical neuron excitability by increasing calcium-activated potassium channels.
Identifies calcium-activated potassium channelopathy as a cause of cortical dysfunction in the PTEN model of autism, providing potential molecular therapeutic targets.
SK channel modulation merits study in PTEN autism models; extends molecular targets but remains hypothesis-generating from animal data.
De novo phosphatase and tensin homolog on chromosome ten (PTEN) mutations are a cause of sporadic autism. How single-copy loss of PTEN alters neural function is not understood. Here we report that Pten haploinsufficiency increases the expression of small-conductance calcium-activated potassium channels. The resultant augmentation of this conductance increases the amplitude of the afterspike hyperpolarization, causing a decrease in intrinsic excitability. In vivo, this change in intrinsic excitability reduces evoked firing rates of cortical pyramidal neurons but does not alter receptive field tuning. The decreased in vivo firing rate is not associated with deficits in the dendritic integration of synaptic input or with changes in dendritic complexity. These findings identify calcium-activated potassium channelopathy as a cause of cortical dysfunction in the PTEN model of autism and provide potential molecular therapeutic targets.
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García‐Junco‐Clemente et al. (2013) studied PTEN-associated autism. Pten haploinsufficiency was evaluated on Expression of small-conductance calcium-activated potassium channels and intrinsic excitability. Pten haploinsufficiency increases the expression of small-conductance calcium-activated potassium channels, decreasing intrinsic excitability and in vivo evoked firing rates of cortical neurons.
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