Progesterone treatment abolishes exogenously expressed ionic currents in Xenopus oocytes

Fully grown oocytes of Xenopus laevis undergo resumption of the meiotic cyc le when treated with the steroid hormone progesterone. Previous studies hav e shown that meiotic maturation results in profound downregulation of speci fic endogenous membrane proteins in oocytes. To determine whether the matur ation impacts the functional properties of exogenously expressed membrane p roteins, we used cut-open recordings from Xenopus oocytes expressing severa l types of Na+ and K+ channels. Treatment of oocytes with progesterone resu lted in a downregulation of heterologously expressed Na+ and K+ channels wi thout a change in the kinetics of the currents. The time course of progeste rone-induced ion channel inhibition was concentration dependent. Complete e limination of Na+ currents temporally coincided with development of germina l vesicle breakdown, while elimination of K+ currents was delayed by simila r to2 h. Coexpression of human beta (1)-subunit with rat skeletal muscle al pha -subunit in Xenopus oocytes did not prevent progesterone-induced downre gulation of Na+ channels. Addition of 8-bromo-cAMP to oocytes or injection of heparin before progesterone treatment prevented the loss of expressed cu rrents. Pharmacological studies suggest that the inhibitory effects of prog esterone on expressed Na+ and K+ channels occur downstream of the activatio n of cdc2 kinase. The loss of channels is correlated with a reduction in Na + channel immunofluorescence, pointing to a disappearance of the ion channe l-forming proteins from the surface membrane.