Electrostatic influences of charged inner pore residues on the conductance and gating of small conductance Ca²⁺ activated K⁺ channels

• Published in: Proceedings of the National Academy of Sciences - PNAS 2011-04, Vol.108 (15), p.5946-5953
• Main Authors: Li, Weiyan, Aldrich, Richard W.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Binding sites; Biological Sciences; Electric current; Electric potential; Electrostatics; Hills equation; Ion Channel Gating; Ion currents; Ions; Large conductance calcium activated potassium channels; Modeling; Molecular Sequence Data; Potassium channels; Small-Conductance Calcium-Activated Potassium Channels - chemistry; Small-Conductance Calcium-Activated Potassium Channels - genetics; Small-Conductance Calcium-Activated Potassium Channels - physiology; Static Electricity
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1103090108

SK channels underlie important physiological functions by linking calcium signaling with neuronal excitability. Potassium currents through SK channels demonstrate inward rectification, which further reduces their small outward conductance. Although it has been generally attributed to block of outward current by intracellular divalent ions, we find that inward rectification is in fact an intrinsic property of SK channels independent of intracellular blockers. We identified three charged residues in the S6 transmembrane domain of SK channels near the inner mouth of the pore that collectively control the conductance and rectification through an electrostatic mechanism. Additionally, electrostatic contributions from these residues also play an important role in determining the intrinsic open probability of SK channels in the absence of Ca²⁺, affecting the apparent Ca²⁺ affinity for activation.