Analysis Tools
mortality/aging
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• all mice die before P40
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• most mice die between P15 and P20
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behavior/neurological
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• tonic-clonic seizure followed by premature death was seen in one mouse and unusual behaviors such as rearing, jumping, and falling are seen in the others, consistent with seizures
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nervous system
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• tonic-clonic seizure followed by premature death was seen in one mouse and unusual behaviors such as rearing, jumping, and falling are seen in the others, consistent with seizures
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• hippocampal membrane fractions show reduced KCNQ3 protein levels by about 60% and KCNQ5 protein levels by about 40%
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• the M current is reduced by about 85%
• CA1 pyramidal neurons show a greater initial firing frequency and a greater final firing frequency, indicating elevated neuronal excitability
• CA1 pyramidal neurons show increased excitability seen as a more than 50% decreased medium afterhyperpolarization and a longer-lasting (2-fold increase) afterdepolarization
• pyramidal neurons fire first in bursts when the depolarization ramp surpasses spike threshold
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• the threshold voltage for action potential generation is shifted to more depolarized membrane potentials, however, this is not accompanied by a decrease in action potential amplitude or in a decrease in the maximum rate of action potential activation
• pyramidal neurons are hyperexcitable, responding to current injections with an increased number and frequency of action potentials
• KCNQ allosteric activators, retigabine and ICA-27243, have only weak effects in pyramidal neurons compared to controls
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• CA1 pyramidal neurons show a more than 50% reduction in medium afterhyperpolarization
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• surface electrocorticography recordings of the cerebral cortex show episodes of polyspike events reaching to about 100 events within the first 15 min compared with hardly any events in controls
• polyspike events show multiple repetitive spikes typically followed by a wave of variable duration, indicating elevated cortical excitability
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