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Gap junctions are specialized membrane channels that connect neighboring animal cells, allowing direct communication between their cytoplasm. They enable the exchange of ions, second messengers, sugars, and other small molecules. This intercellular signaling is essential for coordinated cellular functions across tissues and multicellular organisms.

Six connexin proteins assemble into a hemichannel called a connexon. Two connexons, one from each neighboring cell, pair together to form a complete gap junction channel. These channels cluster into structures called gap junction plaques, which facilitate continuous communication between cells.

Homomeric connexons contain six identical connexin proteins, while heteromeric connexons combine different types of connexins. For example, heart cells can form homomeric connexons with CX40 alone or heteromeric connexons by combining CX40 with CX43. Heteromeric connexons may have different selectivity for specific molecules.

Connexins are first synthesized in the rough endoplasmic reticulum. They then move to the Golgi apparatus, where they assemble into connexons. The cell transports these connexons to the plasma membrane, where they pair with connexons from neighboring cells to form functional gap junction channels.

Gap junctions in the heart allow electrical signals to spread rapidly between cardiomyocytes through direct ion movement. This enables large groups of heart cells to contract together in a coordinated, rhythmic pattern. Under normal conditions, gap junctions remain open to maintain continuous communication essential for proper heartbeat.

Gap junctions possess the ability to switch between open and closed states, allowing cells to regulate molecular exchange. When intracellular calcium levels rise, conformational changes in connexin proteins cause channels to close. This selective permeability is determined by the connexin composition of the channel.

Humans have at least 21 different forms of connexins expressed in almost all cell types. Most cells express more than one connexin type, which can form functional connexon hemichannels or complete gap junction channels. Differential gene expression controls the type and abundance of connexins in various tissues during development and adulthood.