Figure 9.

Proposed function of HCO₃⁻-dependent regulation of KCNQ channels at the AIS. A, Schematic representation of CA3 PC axon initial segment and axo-axonic GABAergic synapse. B, With a depolarized E_GABA, activation of synaptic GABA_A receptors (GABA_ARs) during synaptic GABA release would result in membrane depolarization leading to an increased AP firing probability at the AIS (gray trace). However, local depletion of [HCO₃⁻]_i through GABA_ARs facilitates PIP₂-KCNQ channel interactions and consequently KCNQ channel activity (green arrow). Enhanced KCNQ channel activation dampens excitability at the AIS and reduces AP probability, thus ensuring an inhibitory effect of axoaxonic cell activation despite a depolarized E_GABA (red trace).