Current Research: Voltage sensitive calcium channels are involved in a variety of different physiological processes. Functional channels are formed by the assembly of three subunits. The alpha 1 subunit is the protein through which calcium ions flow, and to which drugs and toxins bind. The alpha 2 subunit and beta subunit are required for channel function, but their role in the channel complex is unclear. We are interested in how these three subunits associate in the formation of the channel complex, and are currently investigating the pathway by which these proteins interact. A second system
we use also focuses on protein-protein interactions and targeting
of proteins to the plasma membrane. Using PCR we have cloned two
potassium channels from mammalian cells, the macrophage inward rectifier
IRK1, and the kidney inward rectifier ROMK1. We are using these
clones in transfected cells to address the issue of how cells sort
and target ion channels to different membrane compartments. We are
also cloning an inward rectifier potassium channel from the polarized
epithelia in colon. This will enable us to have probes for studying
this class of channels in cells which normally express these proteins. Representative Publications: Isom, L.L., K.S. De Jongh, D.E. Patton, B.F.X.Reber, J. Offord, H.Charbonneau, K. Walsh, A.L. Goldin, W.A. Catterall (1992) Primary Structure and Functional Expression of the §1 Subunit of the Rat Brain Sodium Channel. Science 256: 839-842. Duff, H.J., J. Offord, J. West, and W. A. Catterall. (1992) Class I and IV Antiarrhythmic Drugs and Cytosolic Calcium Regulate mRNA Encoding the Sodium Channel Alpha Subunit in Rat Cardiac Muscle. Mol. Pharm. 42: 570-574. Gee, N.S., J. P. Brown, V. U. K. Dissanayake, J. Offord, R. Thurlow, and G. N. Woodruff (1996) The novel anticonvulsant drug, gabapentin, binds to the alpha 2 delta subunit of a calcium channel. J.Biol. Chem. 271: 5768-5776. |