Ionic conductance changes in voltage clamped crayfish axons at low pH

Area of Science:

• Neuroscience
• Biophysics
• Molecular Biology

Background:

• Voltage-clamped crayfish giant axons exhibit ionic currents similar to other nerve cells.
• Understanding ion channel gating mechanisms is crucial for neuroscience.

Purpose of the Study:

• Investigate the effect of external pH on ionic currents in crayfish giant axons.
• Determine the molecular basis for pH-dependent alterations in potassium currents.

Main Methods:

• Voltage clamp technique on crayfish giant axons.
• Systematic variation of external pH and chemical modification of histidine residues.
• Analysis of potassium and sodium currents and conductance-voltage relationships.

Main Results:

• Decreased external pH (below 7) reversibly slowed potassium currents with minimal effect on sodium currents.
• A hyperpolarizing surface charge and altered potassium conductance-voltage curves were observed at low pH.
• Chemical modification of histidine residues mimicked the effects of low pH, implicating histidine titration in altered potassium channel gating.

Conclusions:

• Protonation of histidine residues in membrane proteins significantly impacts potassium channel gating kinetics and conductance.
• Low pH effects involve both electrostatic changes (surface charge) and direct alterations in the protein's chemical interactions governing potassium gate opening/closing.
• A specific histidine residue, closely associated with potassium conductance control, is likely involved.