Phospholamban can act as an ion channel

Phospholamban (PLN) is a major regulator of the sarco- and endoplasmic Ca2+-ATPase (SERCA) and in this context is involved in the contractility of cardiac muscle by regulating the intracellular calcium concentration (Ca2+cyt) of cardiac myocytes. PLN is an integral membrane protein, which exists in equilibrium between monomer and pentamer. Monomeric, unphosphorylated PLN inhibits SERCA, whereas PLN phosphorylation releases the inhibition and allows calcium translocation into sarcoplasmic reticulum. Various details on the structure of PLN in relation to its activity are still a matter of debate[1,2]. Understanding its mode of action remains a major challenge having implications that range from basic protein structure-function studies to clarify heart function and drug development. We combined conductivity measurements on microBLMs and single channel recordings on traditional BLM in order to figure out if the PLN pentamer can have ion channel activity. Both techniques reveal that PLN can act as an ion channel, which is permeable to small ions, e.g. Na+ and K+, but not to bigger choline (Cho+) ion (radius 3,3 A ˚ ). Single channel fluctuations are characterized by two conductance levels, and long open/ closed dwell times in the order of 100 ms. Moreover we provided experimental evidence that the PLN antibody (abPLN) can inhibit the PLN generated channel activity. References: 1 Oxenoid, K. and Chou, J., Proc. Natl. Acad. Sci. U S A. 2005; 102: 10870–10875. 2 Traaseth, N. J., Verardi, R., Torgersen, K. D., Karim, C. B., Thomas, D. D. and Veglia G., Proc. Natl. Acad. Sci. U S A. 2007; 104: 14676–14681.