Regulation of Action Potential Waveforms by Axonal GABA(A) Receptors in Cortical Pyramidal Neurons

GABA(A) receptors distributed in somatodendritic compartments play critical roles in regulating neuronal activities, including spike timing and firing pattern; however, the properties and functions of GABA(A) receptors at the axon are still poorly understood. By recording from the cut end (bleb) of the main axon trunk of layer –5 pyramidal neurons in prefrontal cortical slices, we found that currents evoked by GABA iontophoresis could be blocked by picrotoxin, indicating the expression of GABA(A) receptors in axons. Stationary noise analysis revealed that single-channel properties of axonal GABA(A) receptors were similar to those of somatic receptors. Perforated patch recording with gramicidin revealed that the reversal potential of the GABA response was more negative than the resting membrane potential at the axon trunk, suggesting that GABA may hyperpolarize the axonal membrane potential. Further experiments demonstrated that the activation of axonal GABA(A) receptors regulated the amplitude and duration of action potentials (APs) and decreased the AP-induced Ca(2+) transients at the axon. Together, our results indicate that the waveform of axonal APs and the downstream Ca(2+) signals are modulated by axonal GABA(A) receptors.