{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T01:14:09Z","timestamp":1768439649185,"version":"3.49.0"},"reference-count":86,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T00:00:00Z","timestamp":1594598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The Calmodulin-Cork gating model is based on evidence for the direct role of calmodulin (CaM) in channel gating. Indeed, chemical gating of cell-to-cell channels is sensitive to nanomolar cytosolic calcium concentrations [Ca2+]i. Calmodulin inhibitors and inhibition of CaM expression prevent chemical gating. CaMCC, a CaM mutant with higher Ca2+-sensitivity greatly increases chemical gating sensitivity (in CaMCC the NH2-terminal EF-hand pair (res. 9\u201376) is replaced by the COOH-terminal pair (res. 82\u2013148). Calmodulin colocalizes with connexins. Connexins have high-affinity CaM binding sites. Several connexin mutants paired to wild-type connexins have a high gating sensitivity that is eliminated by inhibition of CaM expression. Repeated transjunctional voltage (Vj) pulses slowly and progressively close a large number of channels by the chemical\/slow gate (CaM lobe). At the single-channel level, the chemical\/slow gate closes and opens slowly with on-off fluctuations. The model proposes two types of CaM-driven gating: \u201cCa-CaM-Cork\u201d and \u201cCaM-Cork\u201d. In the first, gating involves Ca2+-induced CaM-activation. In the second, gating takes place without [Ca2+]i rise. The Ca-CaM-Cork gating is only reversed by a return of [Ca2+]i to resting values, while the CaM-Cork gating is reversed by Vj positive at the gated side.<\/jats:p>","DOI":"10.3390\/ijms21144938","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T09:30:49Z","timestamp":1594719049000},"page":"4938","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Calmodulin-Cork Model of Gap Junction Channel Gating\u2014One Molecule, Two Mechanisms"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7405-1271","authenticated-orcid":false,"given":"Camillo","family":"Peracchia","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology, School of Medicine and Dentistry, University Rochester, Rochester, NY 14642, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Peracchia, C. 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