Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Catterall, William A.
Location University of Washington
Primary Field Physiology and Pharmacology
Secondary Field Cellular and Molecular Neuroscience
 Election Citation
Catterall is a leader in establishing the chemical structure and function of ion channels in excitable cells. Adroitly combining techniques of biochemistry, molecular biology, pharmacology, and electrophysiology, Catterall has characterized the molecular basis of the function of sodium and calcium channels, the key membrane macromolecules responsible for the nerve action potential.
 Research Interests
Electrical impulses generated by ion channels in nerve, skeletal muscle, and heart are essential in coordination of most physiological functions, including learning and memory. We aim to understand the molecular basis of electrical excitability, regulation of electrical excitability by physiological stimuli, and mechanisms underlying diseases and therapies related to electrical signaling. Recently, we have determined the structures of sodium and calcium channels at atomic resolution using X-ray crystallography and cryo-electron microscopy, which has led to a complete structural model for their voltage-dependent activation, ion conductance, and inactivation. We have been able to image binding of local anesthetic, antiarrhythmic, and calcium antagonist drugs at the atomic level. In addition. we have developed a mouse genetic model of Dravet Syndrome, a devastating childhood epilepsy disorder caused by sodium channel mutations. This mouse model recapitulates the multi-faceted deficits of this disease and has led to the conclusion that epilepsy and co-morbidities are caused by selective failure of action potential firing in GABAergic inhibitory neurons. We also study regulation of calcium channels in the heart in the fight-or-flight response and in heart failure, and we use a mouse genetic model to study regulation of presynaptic calcium channels in short-term synaptic plasticity, learning, and memory.

 
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