Ionic blockage of sodium channels in nerve

Area of Science:

• Neuroscience
• Biophysics
• Ion Channel Physiology

Background:

• Sodium permeability is crucial for nerve impulse transmission.
• Voltage-gated sodium channels are key players in neuronal excitability.
• The effects of pH on ion channel function are not fully understood.

Purpose of the Study:

• To investigate the effect of hydrogen ion concentration on sodium permeability in voltage-clamped frog nerves.
• To elucidate the mechanism of voltage-dependent block of sodium channels by hydrogen ions.
• To characterize the binding site and properties of hydrogen ions within the sodium channel.

Main Methods:

• Voltage-clamp electrophysiology on isolated frog nerve fibers.
• Systematic variation of external pH and membrane potential.
• Mathematical modeling to describe ion channel block kinetics.

Main Results:

• Increased hydrogen ion concentration reversibly decreased sodium permeability in a voltage-dependent manner.
• A 60% reduction in sodium permeability was observed at pH 5 and +20 mV, versus 20% at +180 mV.
• A model where hydrogen ions bind within the sodium channel explained the voltage dependence, with a dissociation constant of 3.9 x 10(-6) M (pK(a) 5.4).
• The binding site was localized approximately one-quarter of the way across the membrane potential from the outside.
• Hydrogen ions also shifted sodium channel gating, likely by altering surface potential.

Conclusions:

• Hydrogen ions act as a voltage-dependent blocker of sodium channels in frog nerves by binding within the channel.
• The binding site's location explains the observed voltage dependence of the block.
• Hydrogen ions can also modulate sodium channel gating properties, affecting nerve excitability.