Phospholamban is a Cation Selective Ion Channel

Abstract

Phospholamban (PLN) is a small integral membrane protein, which is involved in the contractility of cardiac muscle by regulating intracellular calcium concentration of cardiac myocytes. PLN binds and inhibits in a yet unknown way the sarco/endoplasmic reticulum Ca2+-ATPase. When reconstituted in planar lipid bilayers PLN exhibits ion channel activity with a main low unitary conductance, a sub-conductance level and a long open/closed dwell time[1]. From the effect of non-electrolyte polymers on this unitary conductance we estimate a narrow pore with a diameter of ca. 2.2 A[2]. This value is similar to that reported for the central pore in the structure of the PLN pentamer[3]. Hence the PLN pentamer, which is in equilibrium with the monomer[4], is the most likely channel forming structure. Moreover, recent data on selectivity show that the channel follows the II Eisenmann sequence (Rb>Cs>K>Na>Li). This pattern reveals that the ion selectivity is regulated by the radius of the binding site and not by the ionic radius. Our results combined with computational data suggest the presence of a selectivity filter in the pentamer PLN.[1] S. Smeazzetto, I. Schroder, G. Thiel, M. R. Moncelli, Phys. Chem. Chem. Phys. 2011, 13, 12935.[2] S. Smeazzetto, A. Saponaro, H. S. Young, M. R. Moncelli, G. Thiel, PLoS One 2013, 8, e52744.[3] K. Oxenoid, J. Chou, Proc. Natl. Acad. Sci. USA 2005, 102, 10870.[4] R. L. Cornea, L. R. Jones, J. M. Autry, D. D. Thomas, Biochemistry. 1997, 36, 2960.The financial support from Ente Cassa di Risparmio di Firenze and Ministero dell'Istruzione, Universita e Ricerca (PRIN project) and from Loewe initiative SoftControl are gratefully acknowledged.