TY - JOUR
T1 - Mechanism of action of quinidine on squid axon membranes
AU - Yeh, J. Z.
AU - Narahashi, T.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1976
Y1 - 1976
N2 - The mechanism of action of quinidine on squid axons has been examined by means of voltage clamp and internal perfusion techniques. When applied either externally or internally, quinidine HCl suppresses both sodium and potassium conductance increases, the effect on the former accounting for the observed decrease in action potential. The potassium conductance in quinidine undergoes a marked inactivation in a manner dependent upon the membrane potential and time, accounting for the observed prolongation of the terminal falling phase of the action potential. Quinidine methiodide exhibits the effect similar to that of quinidine HCl only when applied internally. The dissociation constants of quinidine in suppressing the sodium conducting system are estimated to be 2.4 x 10-4 and 4.0 x 10-4M for quinidine HCl and methiodide, respectively. The dissociation constant of quinidine in suppressing the potassium conducting system decreases with increasing step depolarization. When applied externally to the intact axons, quinidine HCl is more effective at external pH 8.6 than at 7.3. When perfused internally, quinidine HCl is more effective at internal pH 7.0 than at 8.0, and the potency is related to the calculated internal concentration of the charged form rather than that of the uncharged form. These results lead to the conclusion that quinidine HCl penetrates the nerve membrane in the uncharged form, is ionized in the axon and blocks the sodium and potassium conductances primarily in the charged form. Thus, quinidine and local anesthetics share some features in the terms of the site of action and active form.
AB - The mechanism of action of quinidine on squid axons has been examined by means of voltage clamp and internal perfusion techniques. When applied either externally or internally, quinidine HCl suppresses both sodium and potassium conductance increases, the effect on the former accounting for the observed decrease in action potential. The potassium conductance in quinidine undergoes a marked inactivation in a manner dependent upon the membrane potential and time, accounting for the observed prolongation of the terminal falling phase of the action potential. Quinidine methiodide exhibits the effect similar to that of quinidine HCl only when applied internally. The dissociation constants of quinidine in suppressing the sodium conducting system are estimated to be 2.4 x 10-4 and 4.0 x 10-4M for quinidine HCl and methiodide, respectively. The dissociation constant of quinidine in suppressing the potassium conducting system decreases with increasing step depolarization. When applied externally to the intact axons, quinidine HCl is more effective at external pH 8.6 than at 7.3. When perfused internally, quinidine HCl is more effective at internal pH 7.0 than at 8.0, and the potency is related to the calculated internal concentration of the charged form rather than that of the uncharged form. These results lead to the conclusion that quinidine HCl penetrates the nerve membrane in the uncharged form, is ionized in the axon and blocks the sodium and potassium conductances primarily in the charged form. Thus, quinidine and local anesthetics share some features in the terms of the site of action and active form.
UR - http://www.scopus.com/inward/record.url?scp=0017295029&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0017295029&partnerID=8YFLogxK
M3 - Article
C2 - 1518
AN - SCOPUS:0017295029
SN - 0022-3565
VL - 196
SP - 62
EP - 70
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 1
ER -