Modulation of BK Channel Activity by Phosphorylation

The activity of ion channels is frequently modulated by the degree of phosphorylation of either the channel protein itself, or sometimes of an auxiliary regulatory protein. The extent of phosphorylation is maintained through a dynamic balance between phosphorylation by a kinase utilizing ATP and dephosphorylation through the action of a phosphatase. Numerous reports indicate the BK channel contains a number of potential phosphorylation sites, particularly in the carboxy-terminal _tail&Mac246;, and is, in fact, modulated by several different kinases. Whether this regulation increases or decreases channel open probability depends on the particular kinase and on the BK variant being phosphorylated. There is evidence that in some cases a hierarchy of control by different kinases exists. We are investigating whether the potentiation of the BK channel by ethanol is influenced by the extent of phosphorylation. The mouse brain variant, mbr5, is expressed in Xenopus oocytes to maintain a full cell complement of metabolic factors, and channel activity is determined by a two electrode, voltage clamp procedure. Application of cell permeable kinase activators, and kinase and phosphatase inhibitors allow study of modulation of the channel activity itself, and of potential changes in the degree by which ethanol alters this activity.

Education
PhD (Theoretical Chemistry), California Institute of Technology, 1962
BS (Chemistry), Tufts University, 1957

Research Training
National Science Foundation Fellow, Cambridge University, 1962-63.