Abstract
Experiments by the voltage clamp method showed that external application of quinidine (5 × 10−5 M) to the Ranvier node membrane of the frog nerve fiber inhibitis both sodium and potassium currents. Blocking of the sodium current is considerably intensified by repetitive depolarization of the membrane (1–10 Hz); the rate of development of the block increases with an increase in stimulation frequency. After the end of stimulation the sodium current gradually returns to its initial level (with a time constant of the order of 30 sec at 12°C). Unlike repetitive depolarization with short (5 msec) stimuli, a prolonged shift (1 sec) of potential toward depolarization has no significant effect on quinidine blocking of the sodium current. Analysis of the current-voltage characteristic curves showed that quinidine blocks outward sodium current more strongly than inward. Batrachotoxin protects sodium channels against the blocking action of quinidine in a concentration of 10−5 M. Inhibition of the outward potassium currents by quinidine is distinctly time-dependent in character: Initially the potassium current rises to a maximum, then falls steadily to a new stationary level. The results agree with the view that quinidine, applied externally, penetrates through the membrane in the basic form and blocks open sodium and potassium channels from within in the charged (protonated) form. The similarity in principle between the action of quinidine and local anesthetics on the sodium suggests that these compounds bind with the same receptor, located in the inner mouth of the sodium channel.
Similar content being viewed by others
Literature cited
V. M. Bolotina, S. V. Revenko, and B. I. Khodorov, "Stimulus-dependent blockage of sodium channels of the Ranvier node membrane by ethmozin," Neirofiziologiya,13, No. 4, 380 (1981).
L. D. Zaborovskaya and B I. Khodorov, "Stimulus-dependent blockade of sodium channels in the Ranvier node membrane by the quaternary antiarrhythmic N-propylajmaline (neogilurithmal)," Byull. Éksp. Biol. Med.,89, No. 5, 578 (1980).
S. V. Revenko, B. I. Khodorov, and M. Ya. Avrutskii, "The antiarrhythmic cardarone blocks inactivated sodium channels," Byull. Éksp. Biol. Med.,89, No. 7, 702 (1980).
S. V. Revenko, B. I. Khodorov, and L. M. Shapovalova, "Blockade of sodium channels of the Ranvier node membrane by the alkaloid yohimbine," Dokl. Akad. Nauk SSSR,248, No. 2, 494 (1979).
B. I. Khodorov, "Two mechanisms of stimulus-dependence of the action of pharmacologic agents on electrical and contractile activity of myocardial cells," Kardiologiya,20, No. 5, 7 (1980).
M. Cahalan and W. Almers, "Interaction between quaternary lidocaine, the sodium channel gates and tetrodotoxin," Biophys. J.,27, No. 1, 39 (1979).
C. Chen, L. Gettes, and B. Katzung, "Effect of lidocaine and quinidine on steady-state characteristics and recovery kinetics of (dV/dT)max in guinea pig ventricular myocardium," Circ. Res.,37, No. 7, 20 (1976).
F. Dodge and B. Frankenhaeuser, "Sodium currents in the myelinated nerve fiber ofXenopus laevis investigated with the voltage clamp technique," J. Physiol (London),148, No. 2, 188 (1958).
P. Ducouret, "The effect of quinidine on membrane electrical activity in frog auricular fibers studied by current and voltage clamp," Br. J. Pharm.,47, No. 2, 163 (1976).
B. Hille, "Local anesthetics: hydrophilic and hydrophobic pathways for drug-receptor reaction," J. Gen. Physiol.,69, No. 3, 497 (1977).
L. Hondeghem and B. Katzung, "Time- and voltage-dependent interaction of anti-arrhythmic drugs with cardiac sodium channels," Biochim. Biophys. Acta,472, No. 3/4, 373 (1977).
B. Khodorov, "Chemicals as tools to study nerve fibre sodium channels: effects of batrachotoxin and some local anesthetics," in: Membrane Transport Processes, D. Tosteson et al., eds., Raven Press, New York (1978), pp. 153–174.
B. Khodorov, E. Peganov, S. Revenko, and L. Shishkova, "Gating and selectivity of sodium channels in Ranvier node treated with batrachotoxin. Effects of local anesthetics," in: Proc. Int. Union Physiol. Sci., Vol. 12, Paris (1977), p. 195.
B. Khodorov, L. Shishkova, E. Peganov, and S. Revenko, "Inhibition of sodium currents in frog Ranvier node treated with local anesthetics. Role of slow sodium inactivation," Biochim. Biophys. Acta,433, No. 2, 409 (1976).
B. Shapiro, "Effect of strychnine on the sodium conductance of the frog node of Ranvier," J. Gen. Physiol.,69, No. 6, 915 (1977).
O. Strichartz, "The inhibition of sodium currents in myelinated nerve by quaternary derivatives of lidocaine," J. Gen. Physiol.,62, No. 1, 37 (1973).
S. Weidman, "Effects of calcium and local anesthetics on electrical properties of Purkinje fibers," J. Physiol. (London),129, No. 4, 568 (1955).
J. Yeh and T. Narahashi, "Mechanism of action of quinidine on squid axon membranes," J. Pharmacol. Exp. Ther.,196, No. 1, 62 (1976).
L. Zaborovskaya (L. Zaborovskaja) and B. Khodorov, "Stimulus-dependent inhibition of sodium currents by an antiarrhythmic neo-gilurithmal," J. Mol. Cell. Cardiol.,12, Suppl. 1, 185 (1980).
Additional information
A. V. Vishnevskii Institute of Surgery, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 14, No. 3, pp. 324–330, May–June, 1982.
Rights and permissions
About this article
Cite this article
Revenko, S.V., Khodorov, B.I. & Shapovalova, L.M. Quinidine blocking of sodium and potassium channels in myelinated nerve fibers. Neurophysiology 14, 244–250 (1982). https://doi.org/10.1007/BF01065130
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01065130