Electrostatics of the intracellular vestibule of K+ channels.
Previous calculations using continuum electrostatic calculations showed that a fully hydrated monovalent cation is electrostatically stabilized at the center of the cavity of the KcsA potassium channel. Further analysis demonstrated that this cavity stabilization was controlled by a balance between the unfavorable reaction field due to the finite size of the cavity and the favorable electrostatic field arising from the pore helices. In the present study, continuum electrostatic calculations are used to investigate how the stability of an ion in the intracellular vestibular cavity common to known potassium channels is affected as the inner channel gate opens and the cavity becomes larger and contiguous with the intracellular solution. The X-ray structure of the calcium-activated potassium channel MthK, which was crystallized in the open state, is used to construct models of the KcsA channel in the open state. It is found that, as the channel opens, the barrier at the helix bundle crossing decreases to approximately 0 kcal/mol, but that the ion in the cavity is also significantly destabilized. The results are compared and contrasted with additional calculations performed on the KvAP (voltage-activated) and KirBac1.1 (inward rectifier) channels, as well as models of the pore domain of Shaker in the open and closed state. In conclusion, electrostatic factors give rise to energetic constraints on ion permeation that have important functional consequences on the various K+ channels, and partly explain the presence or absence of charged residues near the inner vestibular entry.
Jogini
Vishwanath
V
Department of Physiology & Biophysics, Weill Medical College of Cornell University, New York, NY 10021, USA.
Roux
Benoît
B
D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins / Q000737:chemistry*; D015640:Ion Channel Gating; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000737:chemistry*; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry*; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry*; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D051637:Shaker Superfamily of Potassium Channels / Q000737:chemistry*; D055672:Static Electricity; D014722:Vestibule, Labyrinth / Q000737:chemistry*
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C504448:KcsA protein, Streptomyces coelicolor; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D051637:Shaker Superfamily of Potassium Channels