Abstract
Organic inhibitors of calcium influx prevent outward as well as inward current through cardiac calcium channels but do not slow current activation. Although block is antagonized by raising external calcium or barium concentrations, the competitive effect of permeant cations does not occur at the same cation binding site at which inorganic blockers act. Organic drugs show varying degrees of use-dependent block, due in part to blockade of open channels. Nitrendipine blockade of calcium currents requires doses >100-fold higher than expected from radioligand binding to isolated membranes.
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References
Fleckenstein, A. A. Rev. Pharmac. Tox. 17, 149–166 (1977).
Katz, A. M. & Reuter, H. Am. J. Cardiol. 44, 188–190 (1979).
Triggle, D. J. in Calcium Blockers: Mechanisms of Action and Clinical Applications (eds Flaim, S. F. & Zelis, R. ) 121–134 (Urban & Schwarzenberg, Baltimore, 1982).
Henry, P. D. Am. J. Cardiol. 46, 1047–1058 (1980).
Antman, E. M., Stone, P. H., Muller, J. E. & Braunwald, E. Ann. intern. Med. 93, 875–885 (1980).
Bellemann, P., Ferry, D., Lubbecke, F. & Glossmann, H. Arzneimittel-Forsch. 31, 2064–2067 (1981).
Ehlert, F. J., Itoga, E., Roeske, W. R. & Yamamura, H. Biochem. biophys. Res. Commun. 104, 937–943 (1982).
Gould, R. J., Murphy, K. M. M. & Snyder, S. H. Proc. natn. Acad. Sci. U.S.A. 79, 3656–3660 (1982).
Bolger, G. T. et al. Biochem. biophys. Res. Commun. 104, 1604–160 (1982).
Lee, K. S., Weeks, T. A., Kao, R. L., Akaike, N. & Brown, A. M. Nature 278, 268–271 (1979).
Brown, A. M., Lee, K. S. & Powell, T. J., J. Physiol., Lond. 318, 455–477 (1981).
Lee, K. S. & Tsien, R. W. Nature 297, 498–501 (1982).
Reuter, H. & Scholz, H. J. Physiol., Lond. 264, 17–47 (1977).
Marban, E. & Tsien, R. W. J. Physiol., Lond. 329, 569–587 (1982).
Nawrath, H., Ten Eick, R. E., McDonald, T. F. & Trautwein, W. Circulation Res. 40, 408–414 (1977).
Noma, A. et al. Nature 285, 278–279 (1980).
Isenberg, G. & Klöckner, U. Nature 284, 358–360 (1980).
Powell, T., Terrar, D. A. & Twist, V. W. J. Physiol., Lond. 319, 82–83P (1981).
Hescheler, J., Pelzer, D., Trube, G. & Trautwein, W. Pflügers Arch. ges. Physiol. 393, 287–291 (1982).
Kohlhardt, M., Bauer, B., Krause, H. & Fleckenstein, A. Pflügers Arch. ges. Physiol. 335, 309–322 (1972).
Payet, M. D., Schanne, O.F. & Ruiz-Ceretti, E. J. molec. cell. Cardiol. 12, 635–638 (1980).
Akaike, N., Brown, A. M., Nishi, K. & Tsuda, Y., Br. J. Pharmac. 74, 87–95 (1981).
Hagiwara, S. & Bylerly, L. A. Rev. Neurosci. 4, 69–125 (1981).
Ehara, T. & Kaufmann, R. J. Pharmac. exp. Ther. 207, 49–55 (1978).
McDonald, T. F., Pelzer, D. & Trautwein, W. Pflügers Arch. ges. Physiol. 385, 175–179 (1980).
Kanaya, S. & Katzung, B. G. Circulation 64, IV-274 (1981).
Scheuer, T. & Kass, R. S. Biophys. J. 37, 341a (1982).
Tung, L. & Morad, M. in Ca2+ Entry Blockers, Adenosine, and Neurohumors (ed. Merrill, G.) Ch. 2 (Urban & Schwarzenberg, Baltimore, 1983).
Pelzer, D., Trautwein, W. & McDonald, T. F. Pflügers Arch. ges. Physiol. 394, 97–105 (1982).
Heistracher, P. Naunyn-Schmiedeberg's Archs Pharmak. 269, 199–212 (1971).
Kohlhardt, M. & Fleckenstein, A. Naunyn-Schmiedeberg's Archs Pharmak. 298, 267–272 (1977).
Hille, B. J. gen. Physiol. 69, 497–515 (1977).
Hondeghem, L. M. & Katzung, B. G. Biochim. biophys. Acta 472, 373–398 (1977).
Rodenkirchen, R. et al. Naunyn-Schmiedeberg's Archs Pharmak. 310, 69–78 (1979).
Hess, P., Lee, K. S. & Tsien, R. W. Biophys J. 41, 293a (1983).
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Lee, K., Tsien, R. Mechanism of calcium channel blockade by verapamil, D600, diltiazem and nitrendipine in single dialysed heart cells. Nature 302, 790–794 (1983). https://doi.org/10.1038/302790a0
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DOI: https://doi.org/10.1038/302790a0
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