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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hegyi, Bence Bárándi, László Komáromi, István Papp, Ferenc Horváth, Balázs Magyar, János Bányász, Tamás Krasznai, Zoltán Szentandrássy, Norbert Nánási, Péter P. |
| Description | Country affiliation: Hungary Author Affiliation: Hegyi B ( Department of Physiology, University of Debrecen, P.O. Box 22, 4012, Debrecen, Hungary.) |
| 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. |
| File Format | HTM / HTML |
| ISSN | 00316768 |
| Issue Number | 2 |
| Volume Number | 464 |
| e-ISSN | 14322013 |
| Journal | Pflügers Archiv - European Journal of Physiology |
| Language | English |
| Publisher | Springer |
| Publisher Date | 2012-08-01 |
| Publisher Place | Germany |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Physiology Calcium Channel Blockers Pharmacology Calcium Channels, L-type Drug Effects Myocytes, Cardiac Tetrodotoxin Animals Chemistry Cells, Cultured Dogs Female Heart Ventricles Cytology Male Models, Molecular Metabolism Nav1.5 Voltage-gated Sodium Channel Nisoldipine Patch-clamp Techniques Protein Interaction Domains And Motifs Sodium Channels Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Physiology (medical) Clinical Biochemistry |
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