{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:27:43Z","timestamp":1790515663216,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2016,2,9]],"date-time":"2016-02-09T00:00:00Z","timestamp":1454976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>During each contraction and haemodynamic disturbance, cardiac myocytes are subjected to fluid shear stress as a result of blood flow and the relative movement of sheets of myocytes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The present study aimed to characterize the shear stress\u2010sensitive membrane current in atrial myocytes using the whole\u2010cell patch clamp technique, combined with pressurized fluid flow, as well as pharmacological and genetic interventions of specific proteins.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The data obtained suggest that shear stress indirectly activates the monovalent cation current carried by transient receptor potential melastatin subfamily 4 channels via type 2 inositol 1,4,5\u2010trisphosphate receptor\u2010mediated Ca<jats:sup>2+<\/jats:sup> release in subsarcolemmal domains of atrial myocytes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Ca<jats:sup>2+<\/jats:sup>\u2010mediated interactions between these two proteins under shear stress may be an important mechanism by which atrial cells measure mechanical stress and translate it to alter their excitability.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Atrial myocytes are subjected to shear stress during the cardiac cycle under physiological or pathological conditions. The ionic currents regulated by shear stress remain poorly understood. We report the characteristics, molecular identity and activation mechanism of the shear stress\u2010sensitive current (<jats:italic>I<\/jats:italic><jats:sub>shear<\/jats:sub>) in rat atrial myocytes. A shear stress of \u223c16\u00a0dyn cm<jats:sup>\u22122<\/jats:sup> was applied to single myocytes using a pressurized microflow system, and the current was measured by whole\u2010cell patch clamp. In symmetrical CsCl solutions with minimal concentrations of internal EGTA, <jats:italic>I<\/jats:italic><jats:sub>shear<\/jats:sub> showed an outwardly rectifying current\u2013voltage relationship (reversal at \u22122\u00a0mV). The current was conducted primarily (\u223c80%) by monovalent cations but not Ca<jats:sup>2+<\/jats:sup>. It was suppressed by intracellular Ca<jats:sup>2+<\/jats:sup> buffering at a fixed physiological level, inhibitors of transient receptor potential melastatin subfamily 4 (TRPM4), intracellular introduction of TRPM4 antibodies or knockdown of TRPM4 expression, suggesting that TRPM4 carries most of this current. A notable reduction in <jats:italic>I<\/jats:italic><jats:sub>shear<\/jats:sub> occurred upon inhibition of Ca<jats:sup>2+<\/jats:sup> release through the ryanodine receptors or inositol 1,4,5\u2010trisphosphate receptors (IP<jats:sub>3<\/jats:sub>R) and upon depletion of sarcoplasmic reticulum Ca<jats:sup>2+<\/jats:sup>. In type 2 IP<jats:sub>3<\/jats:sub>R (IP<jats:sub>3<\/jats:sub>R2) knockout atrial myocytes, <jats:italic>I<\/jats:italic><jats:sub>shear<\/jats:sub> was 10\u201320% of that in wild\u2010type myocytes. Immunocytochemistry and proximity ligation assays revealed that TRPM4 and IP<jats:sub>3<\/jats:sub>R2 were expressed at peripheral sites with co\u2010localization, although they are not localized within 40\u00a0nm. Peripheral localization of TRPM4 was intact in IP<jats:sub>3<\/jats:sub>R2 knockout cells. The data obtained in the present study suggest that shear stress activates TRPM4 current by triggering Ca<jats:sup>2+<\/jats:sup> release from the IP<jats:sub>3<\/jats:sub>R2 in the peripheral domains of atrial myocytes.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp270887","type":"journal-article","created":{"date-parts":[[2016,1,11]],"date-time":"2016-01-11T17:24:57Z","timestamp":1452533097000},"page":"2985-3004","source":"Crossref","is-referenced-by-count":25,"title":["Shear stress activates monovalent cation channel transient receptor potential melastatin subfamily 4 in rat atrial myocytes via type 2 inositol 1,4,5\u2010trisphosphate receptors and Ca<sup>2+<\/sup> release"],"prefix":"10.1113","volume":"594","author":[{"given":"Min\u2010Jeong","family":"Son","sequence":"first","affiliation":[{"name":"Laboratory of Physiology, College of Pharmacy Chungnam National University  Yuseong\u2010gu Daejeon South 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