BATRACHOTOXIN-INDUCED DEPOLARIZATION AND [H-3]-LABELED BATRACHOTOXININ-A 20ALPHA-BENZOATE BINDING IN A VESICULAR PREPARATION FROM GUINEA-PIG CEREBRAL-CORTEX - INHIBITION BY LOCAL-ANESTHETICS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 23  (2) , 350-358
Abstract
The Na channel-specific agent batrachotoxin (BTX) induced a time- and concentration-dependent depolarization of a vesicular preparation from guinea pig cerebral cortex. The K0.5 for depolarization by BTX was 0.011 .mu.M at 30 min. Membrane potential was determined by the equilibrium distribution of [3H]triphenylmethylphosphonium ion. A series of 7 local anesthetics inhibited BTX-induced depolarization competitively with Ki [inhibition constant] values ranging from 0.9 .mu.M for dibucaine to 780 .mu.M for lidocaine ethiodide. The specific binding of labeled batrachotoxinin-A 20.alpha.-benzoate ([3H]BTX-B) to voltage-sensitive channels in vesicular preparations from mouse cerebral cortex in the presence of scorpion venom was measured and yielded a range of Kd values from 25-30 nM and Bmax [maximum binding] values of 0.5 and 1.0 pmol/mg of protein; the same preparation from guinea pig cerebral cortex yielded Kd values from 13-56 nM and Bmax values of 0.8-2.2 pmol/mg of protein. A series of 14 local anesthetics inhibited the specific binding of [3H]BTX-B with Ki values ranging from 0.6 .mu.M for dibucaine to 400 .mu.M for benzocaine. The rank order of potency of the local anesthetics as antagonists of [3H]BTX-B binding was as follows: dibucaine > tetracaine > bupivacaine > diphenhydramine > piperocaine > cocaine > procaine > lidocaine > benzocaine. The quarternary local anesthetic dimethyl-di(phenylcarbamoylmethyl)ammonium chloride [QX-572] was comparable in potency to tetracaine. The rank order and relative potency of the local anesthetics tested in both paradigms were similar with the exception of lidocaine ethiodide, which was 18 times more potent as an inhibitor of binding of [3H]BTX-B than it was as an inhibitor of BTX-elicited depolarization. Other anesthetics tested were bupivacaine methiodide, diphenhydramine methiodide and piperocaine methiodide.