Pflügers Archiv

, Volume 335, Issue 4, pp 309–322

Differentiation of the transmembrane Na and Ca channels in mammalian cardiac fibres by the use of specific inhibitors

  • M. Kohlhardt
  • B. Bauer
  • H. Krause
  • A. Fleckenstein
Article

DOI: 10.1007/BF00586221

Cite this article as:
Kohlhardt, M., Bauer, B., Krause, H. et al. Pflugers Arch. (1972) 335: 309. doi:10.1007/BF00586221

Summary

According to earlier studies on mammalian papillary muscles, verapamil and compound D 600 (a methoxy-derivative of verapamil) can abolish the Ca dependent contractile responses completely whilst the Na dependent action potentials persist. In an attempt to clarify the mechanism of action separate measurements of the transmembrane Na and Ca currents have been performed on ventricular trabeculae of cats using a special voltage clamp technique. The following results were obtained:
  1. 1.

    Verapamil (2 mg/l) and compound D 600 (0.5 mg/l) produce a drastic reduction in the transmembrane Ca conductivity. The Ca current can be restored by increasing the extracellular Ca concentration.

     
  2. 2.

    In contrast to their strong inhibitory effects on the passive transmembrane Ca movements verapamil and D 600 in corresponding concentrations do not block the fast Na current.

     
  3. 3.

    Verapamil and D 600 differ in this respect from common local anesthetic compounds such as xylocaine (lidocaine) or procaine which interfere much more with the transmembrane Na conductivity than with the Ca conductivity.

     
  4. 4.

    The selective depression of the Ca or the Na conductivity by specific inhibitors indicates that during excitation the influxes of Na and Ca are independent of each other. Therefore, in the mammalian myocardium the existence of two separate channels for Na and Ca has to be assumed.

     

As a functional significance of this dual membrane transport system it is possible to change the contractile force by inotropic substances which act on the Ca conductivity without a corresponding influence on excitation.

Key words

Transmembrane Ca Current Transmembrane Fast Na Current Excitation Contraction Coupling Selective Inhibitors of Ca or Na Conductivity 

Copyright information

© Springer-Verlag 1972

Authors and Affiliations

  • M. Kohlhardt
    • 1
  • B. Bauer
    • 1
  • H. Krause
    • 1
  • A. Fleckenstein
    • 1
  1. 1.Physiologisches Institut der Universität Freiburg i. Br.Freiburg (Br.)Federal Republic of Germany

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