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Connexins and Pannexins—Similarities and Differences According to the FOD-M Model

ABSTRACT: Connexins and pannexins are the transmembrane proteins of highly distinguished biological activity in the form of transport of molecules and electrical signals. Their common role is to connect the external environment with the cytoplasm of the cell, while connexin is also able to link two cells together allowing the transport from one to another. The analysis presented here aims to identify the similarities and differences between connexin and pannexin. As a comparative criterion, the hydrophobicity distribution in the structure of the discussed proteins was used. The comparative analysis is carried out with the use of a mathematical model, the FOD-M model (fuzzy oil drop model in its Modified version) expressing the specificity of the membrane’s external field, which in the case of the discussed proteins is significantly different from the external field for globular proteins in the polar environment of water. The characteristics of the external force field influence the structure of protein allowing the activity in a different environment.

SUBMITTER: Roterman I

PROVIDER: S-EPMC9313468 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Enhanced gap junctional communication (GJC) between neurons is considered a major factor underlying the neuronal synchrony driving seizure activity. In addition, the hippocampal sharp wave ripple complexes, associated with learning and seizures, are diminished by GJC blocking agents. Although gap junctional blocking drugs inhibit experimental seizures, they all have other non-specific actions. Besides interneuronal GJC between dendrites, inter-axonal and inter-glial GJC is also considered important for seizure generation. Interestingly, in most studies of cerebral tissue from animal seizure models and from human patients with epilepsy, there is up-regulation of glial, but not neuronal gap junctional mRNA and protein. Significant changes in the expression and post-translational modification of the astrocytic connexin Cx43, and Panx1 were observed in an in vitro Co(++) seizure model, further supporting a role for glia in seizure-genesis, although the reasons for this remain unclear. Further suggesting an involvement of astrocytic GJC in epilepsy, is the fact that the expression of astrocytic Cx mRNAs (Cxs 30 and 43) is several fold higher than that of neuronal Cx mRNAs (Cxs 36 and 45), and the number of glial cells outnumber neuronal cells in mammalian hippocampal and cortical tissue. Pannexin expression is also increased in both animal and human epileptic tissues. Specific Cx43 mimetic peptides, Gap 27 and SLS, inhibit the docking of astrocytic connexin Cx43 proteins from forming intercellular gap junctions (GJs), diminishing spontaneous seizures. Besides GJs, Cx membrane hemichannels in glia and Panx membrane channels in neurons and glia are also inhibited by traditional gap junctional pharmacological blockers. Although there is no doubt that connexin-based GJs and hemichannels, and pannexin-based membrane channels are related to epilepsy, the specific details of how they are involved and how we can modulate their function for therapeutic purposes remain to be elucidated.

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Connexins and Pannexins—Similarities and Differences According to the FOD-M Model

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