Trapping Charge Mechanism in Hv1 Channels (CiHv1).

Area of Science:

• Biophysics
• Molecular Biology
• Ion Channel Physiology

Background:

• Voltage-gated ion channels typically have separate voltage-sensing and pore domains.
• The voltage-gated proton channel (Hv1) uniquely combines these functions in a single structural region.
• Understanding Hv1 gating mechanisms is crucial for elucidating electrical excitability.

Purpose of the Study:

• To investigate the voltage sensor trapping mechanism in the voltage-gated proton channel (Hv1).
• To directly measure Hv1 channel gating currents using specific mutations.
• To identify the driving forces behind voltage sensor displacement in Hv1.

Main Methods:

• Utilized site-directed mutagenesis to create Hv1 channel variants.
• Measured Hv1 channel gating currents to track voltage-sensor movements.
• Analyzed the impact of mutations in the selectivity filter and near position 264 on channel gating.

Main Results:

• Voltage sensor displacement in Hv1 is driven by two forces: interactions with the selectivity filter (D160) and electrostatic interactions near position 264.
• Increased hydrophobicity in the selectivity filter raises the energy barrier for voltage sensor activation.
• Positive charges near position 264 facilitate salt bridge formation, stabilizing the voltage sensor conformation.

Conclusions:

• Hv1 voltage sensor activation is governed by a balance of electrostatic and hydrophobic interactions.
• Specific residues, including S4 arginines, N264, and D160 in the selectivity filter, are essential for voltage sensor trapping in *Ciona*-Hv1.
• These findings provide critical insights into the unique gating mechanism of the voltage-gated proton channel.