Ion channel mechanisms underlying frequency-firing patterns of the avian nucleus magnocellularis: A computational model

We have previously shown that late-developing avian nucleus magnocellularis (NM) neurons (embryonic [E] days 19–21) fire action potentials (APs) that resembles a band-pass filter in response to sinusoidal current injections of varying frequencies. NM neurons located in the mid- to high-frequency regions of the nucleus fire preferentially at 75 Hz, but only fire a single onset AP to frequency inputs greater than 200 Hz. Surprisingly, NM neurons do not fire APs to sinusoidal inputs less than 20 Hz regardless of the strength of the current injection. In the present study we evaluated intrinsic mechanisms that prevent AP generation to low frequency inputs. We constructed a computational model to simulate the frequency-firing patterns of NM neurons based on experimental data at both room and near physiologic temperatures. The results from our model confirm that the interaction among low- and high-voltage activated potassium channels (K(LVA) and K(HVA), respectively) and voltage dependent sodium channels (Na(V)) give rise to the frequency-firing patterns observed in vitro. In particular, we evaluated the regulatory role of K(LVA) during low frequency sinusoidal stimulation. The model shows that, in response to low frequency stimuli, activation of large K(LVA) current counterbalances the slow-depolarizing current injection, likely permitting Na(V) closed-state inactivation and preventing the generation of APs. When the K(LVA) current density was reduced, the model neuron fired multiple APs per sinusoidal cycle, indicating that K(LVA) channels regulate low frequency AP firing of NM neurons. This intrinsic property of NM neurons may assist in optimizing response to different rates of synaptic inputs.