title: The effects of extracellular pH with and without bicarbonate on intracellular procaine concentrations and anesthetic effects in crayfish giant axons.
abstract: BACKGROUND
  The potentiating effect of sodium bicarbonate on local anesthetic action is attributed to two mechanisms: (1) an increase in the un-ionized local anesthetic due to extracellular alkalinization, and (2) an accelerated conversion of local anesthetic from un-ionized to ionized form with intracellular acidification caused by bicarbonate. To evaluate these hypotheses, the intracellular pH, intracellular ionized procaine concentration, and evoked action potentials were measured in crayfish giant axons.
  
  
  METHODS
  In all measurements, axon preparations from crayfish were perfused extracellularly for 15 min with either bicarbonate-containing solution at pH 7.6 (bicarb/7.6) or bicarbonate-free solution at pH 7.6 (nonbicarb/7.6) or pH 8.0 (nonbicarb/8.0). Intracellular pH was measured using a pH-sensitive microelectrode. Intracellular anesthetic concentration was measured using a specially designed procaine-sensitive microelectrode with each of three solutions containing 1 mM procaine hydrochloride. Membrane potential was measured and, as an index of anesthetic action, the dV/dt of evoked action potential was calculated during perfusion with procaine.
  
  
  RESULTS
  Mean intracellular pH was significantly lower in the bicarb/7.6 (7.16+/-0.07) group than in the nonbicarb/7.6 (7.33+/-0.09) and nonbicarb/8.0 (7.33+/-0.12) groups (P < 0.01). The mean intracellular ionized procaine concentration was significantly higher in the bicarb/7.6 (0.53+/-0.08 mM; P < 0.05) and nonbicarb/8.0 (0.58+/-0.13 mM; P < 0.01) than in nonbicarb/7.6 (0.32+/-0.14 mM) group but did not differ between the bicarb/7.6 and nonbicarb/8.0 groups. The mean percentage decrease in dV/dtmax was approximately coincident with the mean intracellular procaine concentration in each solution.
  
  
  CONCLUSIONS
  The presence of bicarbonate or extracellular alkalinization increased the intracellular concentration of ionized procaine and the anesthetic effect.
authors.affiliation: Department of Anesthesiology, Miyazaki Medical College, Kiyotake, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ibusuki
authors.forename: H
authors.initials: H
authors.lastname: Katsuki
authors.forename: M
authors.initials: M
authors.lastname: Takasaki
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D003400:Astacoidea; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004357:Drug Synergism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008839:Microelectrodes; D011343:Procaine / Q000493:pharmacokinetics / Q000494:pharmacology*; D017693:Sodium Bicarbonate / Q000494:pharmacology*
chemical_list: D000779:Anesthetics, Local; D011343:Procaine; D017693:Sodium Bicarbonate