Neural blockade by local anesthetics.
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.
D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000494:pharmacology; D005544:Forecasting; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008387:Marine Toxins; D009407:Nerve Block / Q000379:methods*; D009431:Neural Conduction / Q000187:drug effects; D012964:Sodium / Q000378:metabolism
D000779:Anesthetics, Local; D008387:Marine Toxins; D012964:Sodium