Lyotropic anions. Na channel gating and Ca electrode response

Area of Science:

• Neuroscience
• Biophysics
• Ion Channel Physiology

Background:

• Sodium channels are crucial for electrical excitability in muscle and nerve cells.
• External ion concentrations significantly influence the voltage-dependent gating of ion channels.
• Understanding these effects is key to comprehending cellular electrophysiology.

Purpose of the Study:

• To investigate the impact of various external anions on the gating properties of frog skeletal muscle sodium channels.
• To determine the sequence of anion effectiveness in altering sodium channel voltage dependence.
• To elucidate the underlying mechanisms, such as electrostatic interactions and lipid adsorption.

Main Methods:

• Voltage clamp electrophysiology was used to study sodium channel gating.
• A range of external anions (methanesulfonate, chloride, acetate, etc.) were systematically applied.
• Calcium ion (Ca++) activity was measured using the dye murexide and a Ca-sensitive electrode.

Main Results:

• External anions reversibly shifted the voltage dependence of sodium channel activation and inactivation towards more negative potentials.
• The observed shifts followed a lyotropic sequence, correlating with anion charge density and hydrophobicity.
• Anions interfered with calcium-sensitive electrode measurements, with effectiveness mirroring gating shifts, suggesting membrane interactions.

Conclusions:

• Anion adsorption to the sodium channel or surrounding lipid membrane, driven by electrostatic forces, explains the observed gating shifts.
• The lyotropic sequence of anion effectiveness supports the proposed adsorption mechanism.
• Anions also impact calcium electrode measurements due to their membrane permeability, further validating their interaction with hydrophobic environments.