We use biophysical, biochemical, and genetic methods to investigate the functional properties of a family of large-conductance K+ ion channels which are regulated by soluble cytosolic factors. This family includes the widely-distributed BK channel that is regulated by cytosolic Ca2+ and membrane voltage and other family members regulated by cytosolic pH (Slo3) and cytosolic Na+ (Slo2.1 and Slo2.2). Using biophysical approaches coupled with mutational manipulations of the channel genes, we study the underlying mechanisms by which the ion channels are allosterically regulated by ligand and voltage. We also pursue topics concerned with regulation by auxiliary subunits. Finally, we use genetic approaches to delete relevant subunits from in mouse tissues to allow us to address questions concerned with the physiological role of channel subunits. Behavioral studies are employed to assess potential phenotypic consequences of gene deletion.

Biochemistry, Biophysics, and Structural Biology Program Neurosciences Program, ion channel, protein structure, neurobiology, physiology, cell signaling