FoundationalConceptsNeuroscience

used to move energy throughout the body. (Phosphate bonds, espe-
cially ATP, are the primary energy currency inside of cells.) Other
transporters are known to move specific amino acids across the
blood-brain barrier, and still others move other essential molecules.
The second way in which molecules may cross the blood-brain bar-
rier is by dissolving right through the blood vessel cell walls. The cells
that make up the blood vessel walls are bounded, like all cells, with
phospholipid bilayer membrane. In order to dissolve into and pass
through a lipid bilayer membrane, a molecule must be sufficiently
hydrophobic (lipophilic) to comfortably pass through the highly hy-
drophobic central core of the bilayer. Oxygen and other small gaseous
molecules are able to do this. And pretty much all the known drug
molecules that have impact on brain function cross the blood-brain
barrier because they are lipophilic enough to dissolve right through
the cells forming the barrier.
TTX is not sufficiently hydrophobic. It contains many polar
oxygen-hydrogen groups that will attract water molecules, which
prevents it from entering the hydrophobic interior of a lipid bilayer
membrane. Thus, its poison qualities do not impact the functioning of
the brain.
How is it that animals containing TTX are not poisoned by it? I have
already mentioned that the voltage-gated Na channels of the heart
are resistant to the blocking effects of TTX. It turns out that very small
changes in the primary structure of the voltage-gated Na channel (as
little as changing a single amino acid, if it is the right amino acid) can
dramatically reduce its sensitivity to being blocked by TTX. Animals
harboring TTX-producing bacteria have variants of the voltage-gated
Na* channel that are much less affected by TTX. Another place where
this phenomenon occurs is in a species of garter snake that eats newts
containing TTX. Certain populations of this snake have evolved a vari-