Summary
The effects of the calcium antagonist D-600 (methoxyverapamil) on the excitatory inward sodium current,I Na, of internally perfused squid giant axons were studied under voltageclamp conditions. We observed little or no effect of the drug when it was added to the external solution at concentrations of 10–200 μM. Furthermore, it did not produce a frequency, or use-dependent block ofI Na when repetitive voltage-clamp pulses were used at rates of 2–5Hz. However, it did produce use-dependent blockade ofI Na when it was placed internally at a concentration of 200 μM. These results in conjunction with other studies suggest that D-600 is a selective blocker of calcium channels in squid axons when the drug is placed in the external solution. Its effects, when placed in the internal solution, are similar to those of permanently charged local anesthetic derivatives, which also produce use-dependent block ofI Na.
Similar content being viewed by others
References
Baker, P.F., Meves, H., Ridgeway, E.B. 1973. Effects of manganese and other agents on the calcium uptake that follows depolarization of squid axons.J. Physiol. (London) 231:511–526
Bayer, R., Kalusche, D., Kaufmann, R., Mannhold, R. 1975. Inotropic and electrophysiological actions of verapamil and D-600 in mammalian myocardium: III. Effects of the optical isomers on transmembrane action potentials.Naunyn-Schmiedebergs Arch. Pharmakol. 290:81–97
Cahalan, M.D. 1978. Local anesthetic block of sodium channels in normal and pronase treated squid giant axons.Biophys. J. 23:285–311
Clay, J.R., Shlesinger, M.F. 1983. Effects of external cesium and rubidium on outward potassium currents in squid axons.Biophys. J. 42:43–53
Ebihara, L., Shigeto, N., Lieberman, M., Johnson, E.A. 1980. The initial inward current in spherical clusters of chick embryonic heart cells.J. Gen. Physiol. 75:437–456
Frazier, D.T., Narahashi, T., Yamada, M. 1970. The site of action and active form of local anesthetics: II. Experiments with quaternary compounds.J. Pharmacol. Exp. Ther. 171:45–51
French, R.J., Wells, J.B. 1977. Sodium ions as blocking agents and charge carriers in the potassium channel of the squid giant axon.J. Gen. Physiol. 70:707–724
Hille, B. 1977. The pH dependent rate of action of local anesthetics on the node of Ranvier.J. Gen. Physiol. 69:475–496
Hodgkin, A.L., Huxley, A.F. 1952. A quantitative description of membrane current and its application to conduction and excitation in nerve.J. Physiol. (London) 117:500–544
Josephson, I., Sperelakis, N. 1982. On the mechanism underlying adrenergic-cholinergic antagonism in ventricular muscle.J. Gen. Physiol. 79:69–86
Kass, R.S., Tsien, R.W. 1975. Multiple effects of calcium antagonists on plateau currents in cardiac Purkinje fibers.J. Gen. Physiol. 66:169–192
Kohlhardt, M., Bauer, B., Krause, H., Fleckenstein, A. 1972. New selective inhibitors of the transmembrane Ca conductivity in mammalian myocardial fibers: Studies with the voltage clamp technique.Experientia 28:288–289
McDonald, T.F., Pelzer, D., Trautwein, W. 1980. On the mechanism of slow calcium channel block in heart.Pfluegers Arch. 385:175–179
Rosen, M.R., Ilvento, J.P., Gelband, H., Merker, C. 1974. Effects of verapamil on electrophysiologic properties of canine Purkinje fibers.J. Pharmacol. Exp. Ther. 189:414–422
Terakawa, S. 1981. Ca-K bi-ionic action potentials in squid giant axons.J. Membrane Biol. 63:41–50
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Clay, J.R., Shrier, A. Effects of D-600 on sodium current in squid axons. J. Membrain Biol. 79, 211–214 (1984). https://doi.org/10.1007/BF01871060
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01871060