Association of Serine/Threonine Protein Phosphatase Type 2a With Large Conductance Calcium-Activated Potassium (Bk) Channels

Variants of bk-channels that arise through alternative exon splicing have distinct regulatory properties. variants lacking splice inserts (zero) are activated by camp-dependent protein kinase (pka) while those expressing strex-1 at splice site 2 (strex) are inhibited. glucocorticoid hormones block pka- mediated inhibition of strex through a protein phosphatase (pp) but have no effect on zero. as under control conditions pp does not regulate strex, we hypothesized that glucocorticoids could recruit pp to strex. therefore, we have analyzed immunoprecipitates (ips) of bk-channel a-subunits for pp subunit immunoreactivity. the a and c subunits of pp2a were detected in ips from transfected human embryonic kidney 293 cells (hek 293) expressing strex and similar results were obtained in cells expressing zero. ips prepared with an antibody against the a subunit of pp2a contained strex-bk channels. analysis of ips for pp1 c subunit indicated much lower abundance when compared with pp2a. subunits of pp2a also coimmunoprecipitated with bk-channels in extracts of mouse corticotrope tumour cells that predominantly express strex. treatment with dexamethasone did not produce a change for pp2a subunits associated with strex or zero. in summary, pp2a is constitutively associated with strex and zero bk-channels and this is not altered by glucocorticoid treatment.