Abstract

Local anesthetic solutions having different combinations of pCO₂ and pH were applied to sheathed and desheathed frog nerves while recording the compound action potential. CO₂ (1-50%) and local anesthetic (1.0 mM) caused a much greater block when given together than when applied separately. The effect was maximal at a relatively high pH (7.3). The permeability of the nerve sheath to radioactive lidocaine and sucrose was measured while perfusing these substances through a segment of isolated sheath. The apparent permeability to the anesthetic was a linear function of the fraction of nonionized lidocaine and this permeability was not changed by varying pCO₂ or pH. It was concluded that CO₂ potentiates the action of local anesthetics by 1) a direct depressant effect of CO₂ on the axon, 2) concentrating local anesthetic inside the nerve trunk (diffusion trapping) and 3) converting local anesthetic to the active cation through its effect on pH at the site of action inside the nerve.