Effects of Phospholemman Expression on Swelling-Activated Ion Currents and Volume Regulation in Embryonic Kidney Cells

Phospholemman (PLM) is a 72-amino-acid phosphoprotein that is a major substrate for cAMP-dependent protein kinase, protein kinase C, and NIMA kinase. In lipid bilayers, PLM forms ion channels selective for Cl-, K+, and taurine. Effluxes of these abundant intracellular osmolytes play an important role in the control of dynamic cell volume changes in many cell types. We measured swelling-activated ion currents and regulatory volume decrease (RVD) in human embryonic kidney cells stably overexpressing canine cardiac PLM. In response to swelling, two clonal cell lines overexpressing PLM had increased swelling-activated ion current densities and faster and more extensive RVD. A third clonal cell line overexpressing mutant PLM showed reduced ion current densities and a diminished RVD response. These results suggest a role for PLM in the regulation of cell volume, perhaps as a modulator of an endogenous swelling-activated signal transduction pathway or possibly by participating directly in swelling-induced osmolyte efflux.