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. © 2014 the authors.