title: Hippocalcin and KCNQ channels contribute to the kinetics of the slow afterhyperpolarization.
abstract: The calcium-activated slow afterhyperpolarization (sAHP) is a potassium conductance implicated in many physiological functions of the brain including memory, aging, and epilepsy. In large part, the sAHP's importance stems from its exceedingly long-lasting time-course, which integrates action potential-induced calcium signals and allows the sAHP to control neuronal excitability and prevent runaway firing. Despite its role in neuronal physiology, the molecular mechanisms that give rise to its unique kinetics are, to our knowledge, still unknown. Recently, we identified KCNQ channels as a candidate potassium channel family that can contribute to the sAHP. Here, we test whether KCNQ channels shape the sAHP rise and decay kinetics in wild-type mice and mice lacking Hippocalcin, the putative sAHP calcium sensor. Application of retigabine to speed KCNQ channel activation accelerated the rise of the CA3 pyramidal neuron sAHP current in both wild-type and Hippocalcin knockout mice, indicating that the gating of KCNQ channels limits the sAHP activation. Interestingly, we found that the decay of the sAHP was prolonged in Hippocalcin knockout mice, and that the decay was sensitive to retigabine modulation, unlike in wild-type mice. Together, our results demonstrate that sAHP activation in CA3 pyramidal neurons is critically dependent on KCNQ channel kinetics whereas the identity of the sAHP calcium sensor determines whether KCNQ channel kinetics also limit the sAHP decay.
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, USA.
authors.forename: Kwang S
authors.initials: KS
authors.lastname: Kim
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Ken
authors.initials: K
authors.lastname: Takamatsu
authors.forename: Anastasios V
authors.initials: AV
authors.lastname: Tzingounis
mesh_terms: D000818:Animals; D056654:CA3 Region, Hippocampal / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D002219:Carbamates / Q000494:pharmacology; D005260:Female; D055786:Gene Knockout Techniques; D051597:Hippocalcin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051656:KCNQ Potassium Channels / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010655:Phenylenediamines / Q000494:pharmacology
chemical_list: D002219:Carbamates; D051656:KCNQ Potassium Channels; D010655:Phenylenediamines; C101866:ezogabine; D051597:Hippocalcin; D002118:Calcium