The axon initial segment has a unique composition of ion channels that enables action potential initiation. Studying the biophysical properties of this compartment is crucial for understanding neuronal excitability and associated neuronal disorders, including epilepsy. Recently, we found that Ca channels are clustered in the initial segment. Our lab showed that those channels play a critical role in neuronal excitability, and that these channels are subject to dopamine neuromodulation. Modern models of the initial segment includes realistic distributions of Na and K channels, but do not include Ca channels. Here, our goal is to utilize electrophysiological and imaging techniques, both in acute brain slice and heterologous systems, to understand the role of Ca channels in action potential initiation, and to determine how dopaminergic signaling alters the biophysical properties of axonal Ca channels. These data will be incorporated into new models of axon initial segment excitability using novel, GPU-based simulation environments.
The axon initial segment, which is the site of action potential generation in neurons, is comprised of a complex mix of voltage gated channels. Recently, we found that calcium channels play an important role in initial segment excitability. Work here will shed light on their function in this compartment, which may help us understand initial segment-related neuropathies, including epilepsy.
|Ben-Shalom, Roy; Keeshen, Caroline M; Berrios, Kiara N et al. (2017) Opposing Effects on NaV1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures. Biol Psychiatry 82:224-232|
|Yang, Sungchil; Ben-Shalom, Roy; Ahn, Misol et al. (2016) ?-Arrestin-Dependent Dopaminergic Regulation of Calcium Channel Activity in the Axon Initial Segment. Cell Rep 16:1518-1526|