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Updated: May 2, 2026

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting
Published on: December 9, 2022
Intracellular bicarbonate regulates action potential generation via KCNQ channel modulation
Ryan T Jones1, Guido C Faas, Istvan Mody
1Departments of Neurobiology Graduate Program, Departments of Neurology, and Physiology, The David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095.
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.
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