The use of this tetrodotoxin as a
biochemical probe has elucidated two distinct types of voltage-gated sodium
channels present in humans: the tetrodotoxin
-sensitive voltage-gated sodium channel (TTX-s Na+ channel) and the tetrodotoxin
-resistant voltage-gated sodium channel (TTX-r Na+ channel). Nerve cells containing TTX-r Na+ channels are located primarily in cardiac tissue, while
nerve cells containing TTX-s Na+
channels dominate the rest of the body. The prevalence of TTX-s Na+ channels in the central nervous system makes tetrodotoxin a valuable agent for the silencing of neural
activity within a cell culture.
The toxin blocks the fast Na+ current in
human myocytes (the contractile cells of the muscles), inhibiting their contraction. By contrast,
the sodium channels in pacemaker cells of the heart are of the slow variety, so
action potentials in the cardiac nodes are not inhibited by the compound. The
myocytes in the atrium, which surround the main cardiac pacemaker, do express
this fast Na+ current and therefore the electrical activity is blocked and the
heart fails to beat.
Blocking of fast Na+ channels has potential
medical use in treating some cardiac arrhythmias. Tetrodotoxin has proved
useful in the treatment of pain from
such diverse problems as terminal cancer, migraines, and heroin withdrawal.
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