Relationship between pore occupancy and gating in BK potassium channels

Area of Science:

• Molecular Biology
• Biophysics
• Ion Channel Physiology

Background:

• Permeant ions significantly influence ion channel conformational dynamics.
• Understanding ion occupancy effects on gating is crucial for ion channel function.
• BK potassium channels are key regulators of cellular excitability.

Purpose of the Study:

• To investigate the impact of different permeant monovalent cations on BK channel gating.
• To elucidate the relationship between ion permeation and channel conformational changes.
• To characterize the specific effects of thallium on BK channel kinetics and voltage dependence.

Main Methods:

• Macroscopic and single-channel electrophysiological recordings of BK channels.
• Conductance-voltage (GV) curve analysis.
• Kinetic analysis of channel activation and deactivation.
• Allosteric gating model simulations.

Main Results:

• All permeant ions reduced the slope of the conductance-voltage curve compared to potassium.
• Thallium ions uniquely shifted the GV curve, requiring stronger depolarization for channel opening.
• Thallium permeation slowed activation and deactivation kinetics and increased short closing "flicker" events.
• Allosteric modeling indicated thallium specifically affects opening/closing transitions, not voltage or calcium activation pathways.

Conclusions:

• Thallium ions induce unique gating alterations in BK channels, distinct from other monovalent cations.
• The observed effects suggest thallium may stabilize a closed flicker state, potentially mimicking a collapsed selectivity filter.
• These findings provide insights into ion-dependent gating mechanisms and channel structure-function relationships.