Contribution of KCNQ2 and KCNQ3 to the medium and slow afterhyperpolarization currents.
Benign familial neonatal convulsion (BNFC) is a neurological disorder caused by mutations in the potassium channel genes KCNQ2 and KCNQ3, which are thought to contribute to the medium afterhyperpolarization (mAHP). Despite their importance in normal brain function, it is unknown whether they invariably function as heteromeric complexes. Here, we examined the contribution of KCNQ3 and KCNQ2 in mediating the apamin-insensitive mAHP current (ImAHP) in hippocampus. The ImAHP was not impaired in CA1 pyramidal neurons from mice genetically deficient for either KCNQ3 or KCNQ2 but was reduced approximately 50% in dentate granule cells. While recording from KCNQ-deficient mice, we observed that the calcium-activated slow afterhyperpolarization current (IsAHP) was also reduced in dentate granule cells, suggesting that KCNQ channels might also contribute to this potassium current whose molecular identity is unknown. Further pharmacological and molecular experiments manipulating KCNQ channels provided evidence in support of this possibility. Together our data suggest that multiple KCNQ subunit compositions can mediate the ImAHP, and that the very same subunits may also contribute to the IsAHP. We also present data suggesting that the neuronal calcium sensor protein hippocalcin may allow for these dual signaling processes.
Tzingounis
Anastassios V
AV
Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269, USA.
Nicoll
Roger A
RA
D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D020936:Epilepsy, Benign Neonatal / Q000235:genetics; D051597:Hippocalcin / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051658:KCNQ2 Potassium Channel / Q000235:genetics / Q000502:physiology*; D051659:KCNQ3 Potassium Channel / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; C114401:Kcnq2 protein, mouse; C496917:Kcnq3 protein, mouse; D009419:Nerve Tissue Proteins; D051597:Hippocalcin; D001030:Apamin