{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:35:36Z","timestamp":1780590936260,"version":"3.54.1"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH-NIGMS","award":["RO1-GM055437"],"award-info":[{"award-number":["RO1-GM055437"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>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 \u03bcM in the absence of Mg++). They show minimal charge selectivity with respect to small ions (ratio of Na+: K+: Cl\u2212 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\u2212 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.<\/jats:p>","DOI":"10.3390\/life13020390","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T03:22:47Z","timestamp":1675221767000},"page":"390","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Divergence between Hemichannel and Gap Junction Permeabilities of Connexin 30 and 26"],"prefix":"10.3390","volume":"13","author":[{"given":"Ji","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Institute of Neuroscience, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce J.","family":"Nicholson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Structural Biology, University of Texas Health at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41413-020-00126-w","article-title":"Mechanotransduction via the coordinated actions of integrins, PI3K signaling and Connexin hemichannels","volume":"9","author":"Riquelme","year":"2021","journal-title":"Bone Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1096\/fj.00-0566fje","article-title":"Connexin 43 hemi channels mediate Ca2\u00fe-regulated transmembrane NAD\u00fe fluxes in intact cells","volume":"15","author":"Bruzzone","year":"2001","journal-title":"FASEB J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4702","DOI":"10.1523\/JNEUROSCI.5048-07.2008","article-title":"Connexin 43 hemichannels are permeable to ATP","volume":"28","author":"Kang","year":"2008","journal-title":"J. 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