Gap Junction Channel Regulation: A Tale of Two Gates—Voltage Sensitivity of the Chemical Gate and Chemical Sensitivity of the Fast Voltage Gate
Gap junction channels are regulated by gates sensitive to cytosolic acidification and trans-junctional voltage (Vj). We propose that the chemical gate is a calmodulin (CaM) lobe. The fast-Vj gate is made primarily by the connexin’s NH<sub>2</sub>-terminus domain (NT). The chemical gate c...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/2/982 |
| _version_ | 1797339813794283520 |
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| author | Camillo Peracchia |
| author_facet | Camillo Peracchia |
| author_sort | Camillo Peracchia |
| collection | DOAJ |
| description | Gap junction channels are regulated by gates sensitive to cytosolic acidification and trans-junctional voltage (Vj). We propose that the chemical gate is a calmodulin (CaM) lobe. The fast-Vj gate is made primarily by the connexin’s NH<sub>2</sub>-terminus domain (NT). The chemical gate closes the channel slowly and completely, while the fast-Vj gate closes the channel rapidly but incompletely. The chemical gate closes with increased cytosolic calcium concentration [Ca<sup>2+</sup>]<sub>i</sub> and with Vj gradients at Vj’s negative side. In contrast, the fast-Vj gate closes at the positive or negative side of Vj depending on the connexin (Cx) type. Cxs with positively charged NT close at Vj’s negative side, while those with negatively charged NT close at Vj’s positive side. Cytosolic acidification alters in opposite ways the sensitivity of the fast-Vj gate: it increases the Vj sensitivity of negative gaters and decreases that of positive gaters. While the fast-Vj gate closes and opens instantaneously, the chemical gate often shows fluctuations, likely to reflect the shifting of the gate (CaM’s N-lobe) in and out of the channel’s pore. |
| first_indexed | 2024-03-08T09:53:49Z |
| format | Article |
| id | doaj.art-6d702de25e5e42e48fe5d5278652cac3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T09:53:49Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6d702de25e5e42e48fe5d5278652cac32024-01-29T13:55:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-0125298210.3390/ijms25020982Gap Junction Channel Regulation: A Tale of Two Gates—Voltage Sensitivity of the Chemical Gate and Chemical Sensitivity of the Fast Voltage GateCamillo Peracchia0Department of Pharmacology and Physiology, School of Medicine and Dentistry, University Rochester, Rochester, NY 14642-8711, USAGap junction channels are regulated by gates sensitive to cytosolic acidification and trans-junctional voltage (Vj). We propose that the chemical gate is a calmodulin (CaM) lobe. The fast-Vj gate is made primarily by the connexin’s NH<sub>2</sub>-terminus domain (NT). The chemical gate closes the channel slowly and completely, while the fast-Vj gate closes the channel rapidly but incompletely. The chemical gate closes with increased cytosolic calcium concentration [Ca<sup>2+</sup>]<sub>i</sub> and with Vj gradients at Vj’s negative side. In contrast, the fast-Vj gate closes at the positive or negative side of Vj depending on the connexin (Cx) type. Cxs with positively charged NT close at Vj’s negative side, while those with negatively charged NT close at Vj’s positive side. Cytosolic acidification alters in opposite ways the sensitivity of the fast-Vj gate: it increases the Vj sensitivity of negative gaters and decreases that of positive gaters. While the fast-Vj gate closes and opens instantaneously, the chemical gate often shows fluctuations, likely to reflect the shifting of the gate (CaM’s N-lobe) in and out of the channel’s pore.https://www.mdpi.com/1422-0067/25/2/982gap junctionschannelschemical gatingvoltage gatingcalmodulinconnexins |
| spellingShingle | Camillo Peracchia Gap Junction Channel Regulation: A Tale of Two Gates—Voltage Sensitivity of the Chemical Gate and Chemical Sensitivity of the Fast Voltage Gate International Journal of Molecular Sciences gap junctions channels chemical gating voltage gating calmodulin connexins |
| title | Gap Junction Channel Regulation: A Tale of Two Gates—Voltage Sensitivity of the Chemical Gate and Chemical Sensitivity of the Fast Voltage Gate |
| title_full | Gap Junction Channel Regulation: A Tale of Two Gates—Voltage Sensitivity of the Chemical Gate and Chemical Sensitivity of the Fast Voltage Gate |
| title_fullStr | Gap Junction Channel Regulation: A Tale of Two Gates—Voltage Sensitivity of the Chemical Gate and Chemical Sensitivity of the Fast Voltage Gate |
| title_full_unstemmed | Gap Junction Channel Regulation: A Tale of Two Gates—Voltage Sensitivity of the Chemical Gate and Chemical Sensitivity of the Fast Voltage Gate |
| title_short | Gap Junction Channel Regulation: A Tale of Two Gates—Voltage Sensitivity of the Chemical Gate and Chemical Sensitivity of the Fast Voltage Gate |
| title_sort | gap junction channel regulation a tale of two gates voltage sensitivity of the chemical gate and chemical sensitivity of the fast voltage gate |
| topic | gap junctions channels chemical gating voltage gating calmodulin connexins |
| url | https://www.mdpi.com/1422-0067/25/2/982 |
| work_keys_str_mv | AT camilloperacchia gapjunctionchannelregulationataleoftwogatesvoltagesensitivityofthechemicalgateandchemicalsensitivityofthefastvoltagegate |