[Differences in the action of Ca2+ ions on a cumulative Na-channel blockade due to tertiary and quaternary amines].
In voltage-clamp experiments on frog myelinated fibres it has been established that the increase in Ca2+ concentration from 2 to 20 mM does not effect the use-dependent (cumulative) inhibition of sodium channels (INa) produced by the tertiary local anesthetics (lidocaine, tetracaine, etidocaine) and the quaternary antiarrhythmic drug N-propyl ajmaline (NPA). The NPA-induced inhibition of sodium channels does not undergo any essential changes as the (Ca)0 is raised from 2 to 20 mM. On the contrary, the cumulative blockade produced by the tertiary local anesthetics under such an elevation of the (Ca)0 is sharply reduced. This reduction is caused by the inhibitory action of the (Ca)0 on the local anesthetics-induced transition of sodium channels from the state of rapid to slow inactivation. The (Ca)0 does not affect the interaction of the quaternary NPA with open sodium channels. The data obtained provide evidence in favour of the hypothesis about the existence of the different binding sites responsible for cumulative blockade of the INa induced by tertiary and quaternary amines.
Zaborovskaia
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LD
D000588:Amines / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005041:Etidocaine / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008012:Lidocaine / Q000494:pharmacology; D011219:Prajmaline / Q000494:pharmacology; D011895:Rana ridibunda; D011901:Ranvier's Nodes / Q000187:drug effects; D011955:Receptors, Drug / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D013748:Tetracaine / Q000494:pharmacology
D000588:Amines; D007473:Ion Channels; D011955:Receptors, Drug; D013748:Tetracaine; D011219:Prajmaline; D008012:Lidocaine; D012964:Sodium; D005041:Etidocaine; D002118:Calcium
Razlichie v deĭstvii ionov Ca2+ na kumuliativnyĭ blok Na-kanalov, vyzyvaemyĭ tretichnymi i chetvertichnymi aminami.