Neural blockade by local anesthetics
R. H. de Jong
Local anesthetics block nerve impulse propagation by occluding
transmembrane sodium channels, so preventing depolarization. First, the
uncharged lipid-soluble anesthetic base pentrates the membrane; then the
positively charged cation binds to anionic components of the sodium
channel's internal axoplasmic mouth. Though primarily a carrier, the base
contributes to blockade by causing the membrane to swell, so pinching the
sodium channels. Dissolved in water, local anesthetic salt crystals
dissociate into anesthetic cation and base-proportional to the drug's fixed
pKa and the tissue's variable pH. The cation-base concentration ration is
critical to optimal neural blockade. If there is too little base, few
anesthetic molecules will penetrate to the neural target; if too little
cation, few sodium channels will be plugged.