title: Intracellular bicarbonate regulates action potential generation via KCNQ channel modulation.
abstract: Bicarbonate (HCO3(-)) is an abundant anion that regulates extracellular and intracellular pH. Here, we use patch-clamp techniques to assess regulation of hippocampal CA3 pyramidal cell excitability by HCO3(-) in acute brain slices from C57BL/6 mice. We found that increasing HCO3(-) levels enhances action potential (AP) generation in both the soma and axon initial segment (AIS) by reducing Kv7/KCNQ channel activity, independent of pH (i.e., at a constant pH of 7.3). Conversely, decreasing intracellular HCO3(-) leads to attenuation of AP firing. We show that HCO3(-) interferes with Kv7/KCNQ channel activation by phosphatidylinositol-4,5-biphosphate. Consequently, we propose that, even in the presence of a local depolarizing Cl(-) gradient, HCO3(-) efflux through GABAA receptors may ensure the inhibitory effect of axoaxonic cells at the AIS due to activation of Kv7/KCNQ channels.
authors.affiliation: Departments of Neurobiology Graduate Program, Departments of Neurology, and Physiology, The David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Jones
authors.forename: Guido C
authors.initials: GC
authors.lastname: Faas
authors.forename: Istvan
authors.initials: I
authors.lastname: Mody
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism* / Q000494:pharmacology; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051656:KCNQ Potassium Channels / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D001639:Bicarbonates; D051656:KCNQ Potassium Channels