The activation mechanisms of Kv and Nav channels

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DESCRIPTION (provided by applicant): The question of the mechanism of voltage dependent ion channel activation has been a controversial area of interest in recent years. Traditional models of activation have been based primarily on functional and biochemical data from studies on the Shaker potassium channel. While functional data are critical for the understanding of voltage dependent Kv channel physiology, structural data are needed to fully understand the mechanism behind channel activation. The laboratory of Dr. R. MacKinnon published two high resolution crystal structures of the voltage dependent potassium channel, KvAP. With these crystal structures, Dr. MacKinnon's lab published a new model of channel activation, the paddle model, that has many differences from the traditional model. My proposal aims to determine which model best fits the prokaryotic ion channels KvAP and NaChBac by using terbium (Tb3+)-based luminescence resonance energy transfer (LRET) to study the topology and mechanism of activation of KvAP and NaChBac. Voltage dependent ion channels are the underlying causes of diseases in excitatory cells. Thus, it is critical to understand their functional mechanisms in order to understand and treat such disease.