Structure and Functions of Gap Junctions and Their Constituent Connexins in the Mammalian CNS

Abstract

Numerous data obtained in the last 20 years indicate that all parts of the mature central nervous system, from the retina and olfactory bulb to the spinal cord and brain, contain cells connected by gap junctions (GJs). The morphological basis of the GJs is a group of joined membrane hemichannels called connexons, the subunit of each connexon is the protein connexin. In the central nervous system, connexins show specificity and certain types of them are expressed either in neurons or in glial cells. Connexins and GJs of neurons, combining certain types of inhibitory hippocampal and neocortical neuronal ensembles, provide synchronization of local impulse and rhythmic activity, thalamocortical conduction, control of excitatory connections, which reflects their important role in the processes of perception, concentration of attention and consolidation of memory, both on the cellular and at the system level. Connexins of glial cells are ubiquitously expressed in the brain, and the GJs formed by them provide molecular signaling and metabolic cooperation and play a certain role in the processes of neuronal migration during brain development, myelination, tissue homeostasis, and apoptosis. At the same time, mutations in the genes of glial connexins, as well as a deficiency of these proteins, are associated with such diseases as congenital neuropathies, hearing loss, skin diseases, and brain tumors. This review summarizes the existing data of numerous molecular, electrophysiological, pharmacological, and morphological studies aimed at progress in the study of the physiological and pathophysiological significance of glial and neuronal connexins and GJs for the central nervous system.

Keywords: astrocytes; connexins; gap junctions; neurons.

Fig. 1.

Schematic representation of a connexin molecule and a gap junction. (a) The domain structure of one connexin molecule embedded into the membrane lipid bilayer. Designations: M1–M4, transmembrane domains; EL1–EL2, extracellular loops; CL, intracellular loop; NT, N terminus of the molecule; CT, C terminus. (b) Aggregation of individual channels, from 10 to several thousands, results in the formation of a cluster, or a plaque, of gap junctions. The distance between the plaques (transmembrane “gap”) is about 2–3 nm. Each connexon is composed of six connexin molecules (subunits). Types of connexons of the gap junctions: 1, heteromeric heterotypic; 2, homomeric heterotypic; 3, heteromeric homotypic; 4, homomeric homotypic.