Voltage-activated ion channels are expressed in many cells types and are important for an array of physiological processes, including the generation and processing of electrical signals in the nervous system, regulation of heart contraction and secretion of hormones. The role of these channels in electrical signaling is particularly important because they open and close in response to changes in membrane voltage. For example, action potentials result from the orchestrated action of voltage-gated sodium and potassium channels, and voltage-gated calcium channels convert electrical to chemical signals in the process of excitation-secretion coupling. The three main classes of voltage-gated ion channels belong to a common family of membrane proteins constructed from two types of domains: a central pore domain where the conduction pathways for potassium, sodium or calcium ions reside, and four surrounding voltage-sensing domains. A major focus of the lab is to explore the structure of the voltage-sensing domains in voltage-gated potassium (Kv) channels and to define how and where the voltage-sensors interact with the gate region of the pore domain. A complementary aim is to study protein toxins that interact with voltage-gated ion channels. Our work with a class of toxins that we refer to as gating modifier toxins has begun to reveal new mechanisms by which channel-interacting proteins modify activity and to shed light on several fundamental questions concerning the process of voltage-sensing. Since many drugs affecting the nervous system derive their efficacy by modulating the gating of voltage-gated channels, we continue to search for new molecules that interact with these channels and to study the molecular basis for their actions.
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