The connexin family of proteins form hexameric complexes called “connexons”
that facilitate movement of low molecular weight proteins between cells via
gap junctions. Connexin proteins share a common topology of four transmembrane
α-helical domains, two extracellular loops, a cytoplasmic loop and
cytoplasmic N- and C-termini. Many of the key functional differences arise
from specific amino acid substitutions in the most highly conserved domains,
the transmembrane and extracellular regions. Each of the approximately 20
connexin isoforms produces channels with distinct permeabilities and electrical
and chemical sensitivities; therefore, one connexin usually cannot fully
substitute for another. Consequently, a wide variety of malignant phenotypes
associate with decreased connexin expression and gap junction communication,
dependent on the particular connexin that is effected. For instance,
downregulation of connexin 45 in the left ventricle associates with end-stage
heart failure due both