Format

Send to

Choose Destination
Neuron. 2005 Sep 15;47(6):833-43.

The pore helix dipole has a minor role in inward rectifier channel function.

Author information

1
Cardiovascular Research Institute, Department of Biochemistry and Biophysics, California Institute for Quantitative Biomedical Research, University of California, San Francisco, Box 2532, San Francisco, California 94143, USA.

Abstract

Ion channels lower the energetic barrier for ion passage across cell membranes and enable the generation of bioelectricity. Electrostatic interactions between permeant ions and channel pore helix dipoles have been proposed as a general mechanism for facilitating ion passage. Here, using genetic selections to probe interactions of an exemplar potassium channel blocker, barium, with the inward rectifier Kir2.1, we identify mutants bearing positively charged residues in the potassium channel signature sequence at the pore helix C terminus. We show that these channels are functional, selective, resistant to barium block, and have minimally altered conductance properties. Both the experimental data and model calculations indicate that barium resistance originates from electrostatics. We demonstrate that potassium channel function is remarkably unperturbed when positive charges occur near the permeant ions at a location that should counteract pore helix electrostatic effects. Thus, contrary to accepted models, the pore helix dipole seems to be a minor factor in potassium channel permeation.

PMID:
16157278
PMCID:
PMC3017504
DOI:
10.1016/j.neuron.2005.08.022
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center