2-B-P-006 〇山口 陽平^1,2、金子 智之²、入部 玄太郎²、大矢 進¹ Yohei Yamaguchi^1,2, Toshiyuki Kaneko², Gentaro Iribe², Susumu Ohya^{1 1}名古屋市立大・院医・薬理学、²旭川医科大・医・生理学 ¹Dept. Pharmacol. Grad. Sch. Med. Sci. Nagoya City Univ., ²Dept. Physiol. Asahikawa Med. Univ. TRPC6 has been previously reported to be involved in cardiac mechanosensitive responses, e.g., the Anrep effect. However, its role in the Frank-Starling mechanism (FSM) remains unclear. This study investigated whether TRPC6 contributes to the stretch-induced increase in contractile force associated with the FSM. Here, we used isolated ventricular cardiomyocytes from wild-type (WT) and TRPC6^−/− mice hearts. The cells were electrically stimulated at 4 Hz in normal Tyrode solution at 37 °C. Axial stretches were applied using the carbon fibre technique to generate the end-systolic force-length relation (ESFLR) curve. The slope of the ESFLR curve, an indicator of cellular contractility, was significantly steeper in TRPC6^−/− mouse cardiomyocytes than in WT mouse cardiomyocytes. Transcriptome and real-time polymerase chain reaction analysis revealed that the genetic deletion of TRPC6 led to an increase in metallothionein 1 and 2, which is associated with intracellular Zn²⁺ concentrations ([Zn²⁺]_i), along with an increase in ZIP8, a zinc transporter. Subsequently, zinc imaging unveiled an elevation in [Zn²⁺]_i in TRPC6^−/− mouse cardiomyocytes. Interestingly, the addition of Zn²⁺ to the normal Tyrode solution also prompted the contractility in WT mouse cardiomyocytes, while this augmentation was blocked by rac-3, a ZIP8 inhibitor. These results suggest that TRPC6 contributes to alterations in cardiac muscle contractility, associated with the FSM, by regulating [Zn²⁺]_i via ZIP8.