title: Tetrodotoxin blocks L-type Ca2+ channels in canine ventricular cardiomyocytes.
abstract: Tetrodotoxin (TTX) is believed to be the most selective inhibitor of voltage-gated fast Na(+) channels in excitable tissues, including nerve, skeletal muscle, and heart, although TTX sensitivity of the latter is lower than the former by at least three orders of magnitude. In the present study, the TTX sensitivity of L-type Ca(2+) current (I                         (Ca)) was studied in isolated canine ventricular cells using conventional voltage clamp and action potential voltage clamp techniques. TTX was found to block I                         (Ca) in a reversible manner without altering inactivation kinetics of I                         (Ca). Fitting results to the Hill equation, an IC(50) value of 55 ± 2 μM was obtained with a Hill coefficient of unity (1.0 ± s0.04). The current was fully abolished by 1 μM nisoldipine, indicating that it was really I                         (Ca). Under action potential voltage clamp conditions, the TTX-sensitive current displayed the typical fingerprint of I                         (Ca), which was absent in the presence of nisoldipine. Stick-and-ball models for Cav1.2 and Nav1.5 channel proteins were constructed to explain the differences observed between action of TTX on cardiac I                         (Ca) and I                         (Na). This is the first report demonstrating TTX to interact with L-type calcium current in the heart.
authors.affiliation: Department of Physiology, University of Debrecen, P.O. Box 22, 4012, Debrecen, Hungary.
authors.forename: Bence
authors.initials: B
authors.lastname: Hegyi
authors.forename: László
authors.initials: L
authors.lastname: Bárándi
authors.forename: István
authors.initials: I
authors.lastname: Komáromi
authors.forename: Ferenc
authors.initials: F
authors.lastname: Papp
authors.forename: Balázs
authors.initials: B
authors.lastname: Horváth
authors.forename: János
authors.initials: J
authors.lastname: Magyar
authors.forename: Tamás
authors.initials: T
authors.lastname: Bányász
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Krasznai
authors.forename: Norbert
authors.initials: N
authors.lastname: Szentandrássy
authors.forename: Péter P
authors.initials: PP
authors.lastname: Nánási
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000187:drug effects*; D002478:Cells, Cultured; D004285:Dogs; D005260:Female; D006352:Heart Ventricles / Q000166:cytology; D008297:Male; D008958:Models, Molecular; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015737:Nisoldipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D054730:Protein Interaction Domains and Motifs; D015222:Sodium Channels / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C); D062554:NAV1.5 Voltage-Gated Sodium Channel; D015222:Sodium Channels; D013779:Tetrodotoxin; D015737:Nisoldipine