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Effects of Tetrodotoxin on the Mammalian Cardiovascular System
Institute of Physiology II, Friedrich Schiller University, Kollegiengasse 9, 07743 Jena, Germany
Received: 3 February 2010; in revised form: 11 February 2010 / Accepted: 18 March 2010 / Published: 19 March 2010
Abstract: The human genome encodes nine functional voltage-gated Na+ channels. Three of them, namely Nav1.5, Nav1.8, and Nav1.9, are resistant to nanomolar concentrations of tetrodotoxin (TTX; IC50 ≥ 1 μM). The other isoforms, which are predominantly expressed in the skeletal muscle and nervous system, are highly sensitive to TTX (IC50 ~ 10 nM). During the last two decades, it has become evident that in addition to the major cardiac isoform Nav1.5, several of those TTX sensitive isoforms are expressed in the mammalian heart. Whereas immunohistochemical and electrophysiological methods demonstrated functional expression in various heart regions, the physiological importance of those isoforms for cardiac excitation in higher mammals is still debated. This review summarizes our knowledge on the systemic cardiovascular effects of TTX in animals and humans, with a special focus on cardiac excitation and performance at lower concentrations of this marine drug. Altogether, these data strongly suggest that TTX sensitive Na+ channels, detected more recently in various heart tissues, are not involved in excitation phenomena in the healthy adult heart of higher mammals.
Keywords: Na+ channel; TTX sensitivity; cardiac conduction; TTX poisoning
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Cite This Article
MDPI and ACS Style
Zimmer, T. Effects of Tetrodotoxin on the Mammalian Cardiovascular System. Mar. Drugs 2010, 8, 741-762.
Zimmer T. Effects of Tetrodotoxin on the Mammalian Cardiovascular System. Marine Drugs. 2010; 8(3):741-762.
Zimmer, Thomas. 2010. "Effects of Tetrodotoxin on the Mammalian Cardiovascular System." Mar. Drugs 8, no. 3: 741-762.