Sodium channel selectivity and conduction: prokaryotes have devised their own molecular strategy

Area of Science:

• Structural biology
• Ion channel biophysics
• Computational neuroscience

Background:

• Prokaryotic and eukaryotic voltage-gated sodium (Nav) channels exhibit significant structural differences, suggesting divergent molecular mechanisms.
• Despite structural disparities, both channel families display similar alkali cation selectivity sequences and reversal potentials under reversed Na/K gradients.

Purpose of the Study:

• To investigate the molecular mechanisms underlying ion selectivity in prokaryotic Nav channels.
• To compare the ion binding and permeation properties of prokaryotic Nav channels with those of eukaryotic Nav, Ca2+, and K+ channels.

Main Methods:

• Experimental studies on prokaryotic Nav channels NaChBac and NavAb, including ion selectivity measurements and pH-dependent and mutant analyses.
• Atomistic simulations based on the NavAb crystal structure to determine energetic contributions to ion selectivity.
• Analysis of ion-ion interactions and potentials of mean force within the channel pore.

Main Results:

• NaChBac exhibits anomalous nonmonotonic mole-fraction dependence in Na/K mixtures, unlike eukaryotic Nav channels.
• Prokaryotic Nav channel selectivity for sodium is modulated by selectivity filter charge and steric perturbations.
• Simulations reveal that a thermodynamic penalty for K+ binding and inter-ion interactions contribute to Na+ selectivity in wild-type channels.

Conclusions:

• Prokaryotic Nav channels employ a selectivity strategy involving tight single-ion binding and crucial inter-ion interactions.
• This prokaryotic Nav channel mechanism more closely resembles that of eukaryotic Ca2+ and K+ channels than eukaryotic Nav channels.