Selectivity of the phospholamban ion channel investigated by single channel measurements

Phospholamban (PLN) is a small integral membrane protein, which is involved in the contractility of cardiac muscle. PLN has a dual function: the monomer inhibits Ca2+ transport by the sarcoplasmic reticulum Ca-ATPase (SERCA). In its pentameric form it generates an ion channel, which presumably contributes to a modulation of SERCA activity by balancing the charge generated by Ca2+ uptake into the sarcoplasmic reticulum. The PLN channel is characterized by a low unitary conductance, a sub-conductance and long open/closed dwell times. In this study we investigated the ion selectivity of the PLN channel. PLN is selective for monovalent cations and not permeable to divalent cations (Ca2+ and Ba2+) and anions (chloride and phosphate) over the voltage range investigated. The selectivity for monovalent cations is not determined by ionic radius but it probably involves a well-regulated mechanism of interaction between permeant ions and the binding site(s) in the PLN-generated channel. The finding that the cation selectivity follows the second Eisenman series (Rb > Cs > K > Na > Li) indicates that selectivity is mostly determined by the difference in energy required to remove water from a fully hydrated cation.