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Life (Basel) 2023 Jan 31;132:. doi: 10.3390/life13020390.
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Divergence between Hemichannel and Gap Junction Permeabilities of Connexin 30 and 26.

Xu J , Nicholson BJ .

Cx30 has been proposed to play physiological functions in the kidney and cochlea, and this has often been associated with its hemichannel role (deafness mutants frequently affecting hemichannels more than gap junctions), implicated in ATP release. Here, we used heterologous expression systems (Xenopus oocytes and N2A cells) to describe the properties of Cx30 hemichannels, with the objective of better understanding their physiological functions. As previously observed, Cx30 hemichannels gated in response to transmembrane voltage (V0) and extracellular [Ca2+] (pK[Ca2+] of 1.9 μM in the absence of Mg++). They show minimal charge selectivity with respect to small ions (ratio of Na+: K+: Cl- of 1: 0.4: 0.6) and an MW cut-off for Alexa Dyes between 643 (Alex 488) and 820 Da (Alexa 594). However, while cations follow the expected drop in conductance with size (Na+ to TEA+ is 1: 0.3), anions showed an increase, with a ratio of Cl- to gluconate conductance of 1:1.4, suggesting favorable interactions between larger anions and the pore. This was further explored by comparing the permeabilities of both hemichannels and gap junctions to the natural anion (ATP), the release of which has been implicated in Ca++ signaling through hemichannels. We extended this analysis to two closely related connexins co-expressed in the cochlear, Cx26 and Cx30. Cx30 and 26 hemichannels displayed similar permeabilities to ATP, but surprisingly Cx26 gap junctions were six times more permeable than their hemichannels and four times more permeable than Cx30 gap junctions. This suggests a significant physiological difference in the functions of Cx26 and Cx30 gap junctions in organs where they are co-expressed, at least with regard to the distribution of energy resources of the cells. It also demonstrates that the permeability characteristics of hemichannels can significantly diverge from that of their gap junctions for some connexins but not others.

PubMed ID: 36836746
PMC ID: PMC9962233
Article link: Life (Basel)
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: gjb1 gjb2
GO keywords: calcium channel activity

Article Images: [+] show captions
References [+] :
Anselmi, ATP release through connexin hemichannels and gap junction transfer of second messengers propagate Ca2+ signals across the inner ear. 2008, Pubmed