An unexpected role for brain-type sodium channels in coupling of
cell surface depolarization to contraction in the heart.
Proc. Natl. Acad. Sci. U. S. A., 99 (6):
4073--4078 (March 2002)DOI: 10.1073/pnas.261705699
Abstract
Voltage-gated sodium channels composed of pore-forming alpha and auxiliary
beta subunits are responsible for the rising phase of the action
potential in cardiac muscle, but the functional roles of distinct
sodium channel subtypes have not been clearly defined. Immunocytochemical
studies show that the principal cardiac pore-forming alpha subunit
isoform Na(v)1.5 is preferentially localized in intercalated disks,
whereas the brain alpha subunit isoforms Na(v)1.1, Na(v)1.3, and
Na(v)1.6 are localized in the transverse tubules. Sodium currents
due to the highly tetrodotoxin (TTX)-sensitive brain isoforms in
the transverse tubules are small and are detectable only after activation
with beta scorpion toxin. Nevertheless, they play an important role
in coupling depolarization of the cell surface membrane to contraction,
because low TTX concentrations reduce left ventricular function.
Our results suggest that the principal cardiac isoform in the intercalated
disks is primarily responsible for action potential conduction between
cells and reveal an unexpected role for brain sodium channel isoforms
in the transverse tubules in coupling electrical excitation to contraction
in cardiac muscle.
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