{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T01:24:31Z","timestamp":1783819471958,"version":"3.55.0"},"reference-count":54,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"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>L-type Ca2+ channels, particularly CaV1.2, play a crucial role in cardiac excitation-contraction coupling and are known to exhibit mechanosensitivity. However, the mechanisms regulating their response to mechanical stress remain poorly understood. To investigate the mechanosensitivity and nitric oxide (NO)-dependent regulation of L-type Ca2+ channels in rat ventricular cardiomyocytes, we used RNA sequencing to assess isoform expression and whole-cell patch-clamp recordings to measure L-type Ca2+ current (ICa,L) under controlled mechanical and pharmacological conditions. RNA sequencing revealed predominant expression of CaV1.2 (TPM: 0.1170 \u00b1 0.0075) compared to CaV1.3 (0.0021 \u00b1 0.0002) and CaV1.1 (0.0002 \u00b1 0.0002). Local axial stretch (6\u201310 \u03bcm) consistently reduced ICa,L in proportion to stretch magnitude. The NO donor SNAP (200 \u03bcM) had variable effects on basal ICa,L in unstretched cells (stimulatory, inhibitory, or biphasic) but consistently restored stretch-reduced ICa,L to control levels. Ascorbic acid (10 \u03bcM), which reduces S-nitrosylation, increased basal ICa,L and partially restored the reduction caused by stretch, implicating S-nitrosylation in channel regulation. The sGC inhibitor ODQ (5 \u03bcM) decreased ICa,L in both stretched and unstretched cells, indicating involvement of the NO\u2013cGMP pathway. Mechanical stress modulates L-type Ca2+ channels through a complex interplay between S-nitrosylation and NO\u2013cGMP signaling, with S-nitrosylation playing a predominant role in stretch-induced effects. This mechanism may represent a key component of cardiac mechanotransduction and could be relevant for therapeutic targeting in cardiac pathologies involving mechanically induced dysfunction.<\/jats:p>","DOI":"10.3390\/ijms26157539","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T07:45:11Z","timestamp":1754466311000},"page":"7539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mechanotransduction-Driven Modulation of L-Type Calcium Channels: Roles of Nitric Oxide, S-Nitrosylation, and cGMP in Rat Ventricular Cardiomyocytes"],"prefix":"10.3390","volume":"26","author":[{"given":"Olga V.","family":"Kamkina","sequence":"first","affiliation":[{"name":"Institute of Physiology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia S.","family":"Rodina","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Kamkin","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei S.","family":"Bilichenko","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor E.","family":"Kazansky","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra D.","family":"Zolotareva","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin I.","family":"Zolotarev","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislav A.","family":"Shileiko","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim M.","family":"Mitrokhin","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3475-2131","authenticated-orcid":false,"given":"Mitko I.","family":"Mladenov","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/415198a","article-title":"Cardiac excitation\u2013contraction coupling","volume":"415","author":"Bers","year":"2002","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"C1001","DOI":"10.1152\/ajpcell.00140.2002","article-title":"\u03b1(1C) (Ca(v)1.2) L-type calcium channel mediates mechanosensitive calcium regulation","volume":"283","author":"Lyford","year":"2002","journal-title":"Am. 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