The kinetics of local anesthetic blockade of end-plate channels.
The effect of the local anesthetic QX222 on the kinetics of miniature end-plate currents (MEPC)and acetylcholine-induced end-plate current fluctuations was studied in voltage-clamped frog cutaneous pectoris neuromuscular junctions. The rate constants for a kinetic scheme of local anesthetic blockage of end-plate channels were calculated from the MEPC decay parameters. At 18 degrees C the blocking rate constant was 1.1 +/- 0.3 x 10(7) exp (-0.009 +/- 0.003 x V)s -1M-1, and the unblocking rate constant was 5.7 +/- 0.6 exp (0.011 +/- 0.002 x V)s -1. The dissociation constant was close to 10 microM at -80 mV. End-plate fluctuations indicated that the local anesthetic QX222 lowered the effective single-channel conductance, suggesting a finite blocked state conductance that was calculated to be 1.6 pS. The apparent differences between QX222 interaction with end-plate and extrajunctional channels are discussed.
D000779:Anesthetics, Local; D000818:Animals; D005374:Filtration; D007700:Kinetics; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000378:metabolism; D008433:Mathematics; D009469:Neuromuscular Junction / Q000187:drug effects*; D011894:Rana pipiens
D000779:Anesthetics, Local; C006072:QX-222; D008012:Lidocaine