Tetrodotoxin blocks native cardiac L-type calcium channels but not Cav1.2 channels expressed in hek cells

N. Szentandrassy, F. Papp, B. Hegyi, A. Bartok, Z. Krasznai, Peter P. Nanasi

Research output: Article

11 Citations (Scopus)

Abstract

Tetrodotoxin (TTX) has been believed for a long time to be a selective inhibitor of voltage-gated fast Na+ channels in excitable tissues, including mammalian myocardium. Recently TTX has been shown to block cardiac L-type Ca2+ current (ICa,L). Furthermore, this inhibition was ascribed to binding of TTX to the outer pore of the Ca2+ channel, contributing to the selectivity filter region. In this study the TTX-sensitivity of Cav1.2 channels, expressed in HEK cells, was tested using the whole cell version of the patch clamp technique and compared to the TTX-sensitivity of native canine ICa,L. Cav1.2 channels mediate Ca2+ current in ventricular myocardium of various mammalian species. Surprisingly, TTX failed to inhibit Cav1.2 current up to the concentration of 100 μM - in contrast to ICa,L - in spite of the fact that the kinetic properties of the ICa,L and Cav1.2 currents were similar. The possible reasons for this discrepancy are discussed. Present results may question the suitability of a single pore-forming channel subunit, expressed in a transfection system, for electrophysiological or pharmacological studies.

Original languageEnglish
JournalJournal of Physiology and Pharmacology
Volume64
Issue number6
Publication statusPublished - dec. 2013

ASJC Scopus subject areas

  • Physiology
  • Pharmacology

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