Gap Junctions Allow Ions and Small Molecules to Flow between Communicating Cells

I. The Molecular Design of Life
13. Membrane Channels and Pumps
13.6. Gap Junctions Allow Ions and Small Molecules to Flow between
Communicating Cells
The ion channels that we have considered thus far have narrow pores and are moderately to highly selective in regard to
which ions are permeant. They are closed in the resting state and have short lifetimes in the open state, typically a
millisecond, that enable them to transmit highly frequent neural signals. We turn now to a channel with a very different
role. Gap junctions, also known as cell-to-cell channels, serve as passageways between the interiors of contiguous cells.
Gap junctions are clustered in discrete regions of the plasma membranes of apposed cells. Electron micrographs of
sheets of gap junctions show them tightly packed in a regular hexagonal array (Figure 13.30A). A 20-Å central hole, the
lumen of the channel, is prominent in each gap junction. A tangential view (Figure 13.30B) shows that these channels
span the intervening space, or gap, between apposed cells (hence, the name gap junction). The width of the gap between
the cytosols of the two cells is about 35 Å.
Small hydrophilic molecules as well as ions can pass through gap junctions. The pore size of the junctions was
determined by microinjecting a series of fluorescent molecules into cells and observing their passage into adjoining cells.
All polar molecules with a mass of less than about 1 kd can readily pass through these cell-to-cell channels. Thus,
inorganic ions and most metabolites (e.g., sugars, amino acids, and nucleotides) can flow between the interiors of cells
joined by gap junctions. In contrast, proteins, nucleic acids, and polysaccharides are too large to traverse these channels.
Gap junctions are important for intercellular communication. Cells in some excitable tissues, such as heart muscle, are
coupled by the rapid flow of ions through these junctions, which ensure a rapid and synchronous response to stimuli.
Gap junctions are also essential for the nourishment of cells that are distant from blood vessels, as in lens and bone.
Moreover, communicating channels are important in development and differentiation. For example, a pregnant uterus is
transformed from a quiescent protector of the fetus to a forceful ejector at the onset of labor; the formation of functional
gap junctions at that time creates a syncytium of muscle cells that contract in synchrony.
A cell-to-cell channel is made of 12 molecules of connexin, one of a family of transmembrane proteins with molecular
masses ranging from 30 to 42 kd. Each connexin molecule appears to have four membrane-spanning helices. Six
connexin molecules are hexagonally arrayed to form a half channel, called a connexon or hemichannel (Figure 13.31).
Two connexons join end to end in the intercellular space to form a functional channel between the communicating cells.
Cell-to-cell channels differ from other membrane channels in three respects: (1) they traverse two membranes rather than
one; (2) they connect cytosol to cytosol, rather than to the extracellular space or the lumen of an organelle; and (3) the
connexons forming a channel are synthesized by different cells. Gap junctions form readily when cells are brought
together. A cell-to-cell channel, once formed, tends to stay open for seconds to minutes. They are closed by high
2+
+
and H serves to seal normal cells
concentrations of calcium ion and by low pH. The closing of gap junctions by Ca
from traumatized or dying neighbors. Gap junctions are also controlled by membrane potential and by hormone-induced
phosphorylation.
I. The Molecular Design of Life
13. Membrane Channels and Pumps
13.6. Gap Junctions Allow Ions and Small Molecules to Flow between Communicating Cells
Figure 13.30. Gap Junctions. (A) This electron micrograph shows a sheet of isolated gap junctions. The cylindrical
connexons form a hexagonal lattice having a unit-cell length of 85 Å. The densely stained central hole has a diameter of
about 20 Å. (B) Electron micrograph of a tangential view of apposed cell membranes that are joined by gap junctions.
[(A) Courtesy of Dr. Nigel Unwin and Dr. Guido Zampighi; (B) from E. L. Hertzberg and N. B. Gilula. J. Biol. Chem.
254(1979):2143.]
I. The Molecular Design of Life
13. Membrane Channels and Pumps
13.6. Gap Junctions Allow Ions and Small Molecules to Flow between Communicating Cells
Figure 13.31. Schematic Representation of a Gap Junction. [Courtesy of Dr. Werner Loewenstein.]