Two recent papers published in the Journal of General Physiology (Guo and Lu, 2003; Guo et al., 2003) address the mechanism of inward rectification by polyamines in Kir2.1 channels. In these two papers, Guo et al. (2003) extensively analyze channel block by monoamines, diamines (DAs), and polyamines of varying length and charge, using thermodynamic mutant cycles to calculate interaction energies of these compounds with acidic residues in the channel. Based on their findings, a physical model for the blocking action of polyamines is proposed that incorporates the most recent structural information determined for Kir channels.
We write to suggest a different and, in our view, more plausible physical interpretation, which we believe better reconciles their results with previous electrophysiological as well as structural findings (Pearson and Nichols, 1998; Kubo and Murata, 2001; Xie et al., 2002, 2003;...
