MECHANISMS OF BUPIVACAINE ACTION ON NA-LAEVIS( AND K+ CHANNELS IN MYELINATED AXONS OF XENOPUS)

The local anaesthetic bupivacaine has recently been proposed to inhibi t Na+ channels indirectly by making the resting potential less negativ e. To test this hypothesis we analysed the effects of bupivacaine on v oltage and current clamped nodes of Ranvier. Contrary to the hypothesi s, the leak current and the resting potential were unaffected. The Na and K+ channels were, however, affected at relatively low concentrati ons (33 mu M). Steady-state activation curves were decreased without n otable shift effects, whereas the Naf inactivation curve was decreased and shifted in negative direction. The effect on the Na+ current was tentatively explained by a single-site, state-dependent binding model (K-d = 44 mu M), while that on the K+ current was explained by two pop ulation-specific mechanisms, one open-state dependent (K-d = 550 mu M) and one state independent (K-d = 59 mu M). The binding stoichiometry was higher than 1:1 for the main sites of action. In conclusion, bupiv acaine exerts its main anaesthetic action on myelinated nerve axons by a direct modification of Na+ channels. (C) 1998 Elsevier Science B.V. All rights reserved.