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- W3004651812 abstract "An increase in preload induces a biphasic response in the heart. The short-term increase in preload rapidly augments contractile force owing to the Frank-Starling mechanism (FSM) that accelerates Ca2+ sensitivity of the contraction protein. A further long-term increase in preload for several minutes causes the increase in [Ca2+]i, leading to slow force response to stretch (SFR), a further increase in the contractile force. The authors’ previous study identified the involvement of TRPC3 and TRPC6, mechanosensitive non-selective cation channels, in SFR. However, the participation of TRPC3 and TRPC6 in FSM remains unclear. To clarify the role of TRPC3 and TRPC6 in FSM, cardiomyocytes were enzymatically isolated from either wild-type (WT), TRPC3 knockout (KO), or TRPC6 KO mice. Both cell ends were held by two pairs of carbon fibers attached to both upper and bottom cell surfaces to apply stretch to the cells. The cells were paced at 4 Hz and superfused in normal Tyrode solution at 37 °C. Cell length and active/passive force calculated from carbon fiber bending were recorded in six different preload conditions. The effect of each genetic deletion on cellular contractility and elastance was assessed by the slope of end-systolic force-length relation curve (ESFLR) and end-diastolic force-length relation curve (EDFLR). The slope of ESFLR was significantly steeper in TRPC6 KO mice than in WT mice, though it remained unchanged in TRPC3 KO mice (0.47 ± 0.1; 0.35 ± 0.14; 0.36 ± 0.14 mN∙mm−2∙μm−1). Meanwhile, the slope of EDFLR was not significantly different between WT, TRPC3 KO, and TRPC6 KO mice (0.16 ± 0.046; 0.19 ± 0.11; 0.19 ± 0.13 mN∙mm−2∙μm−1). These results suggest that TRPC6 regulates the contractile property via modulating the increase in the contractile force controlled by FSM, while TRPC3 is not involved in FSM." @default.
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- W3004651812 date "2020-02-01" @default.
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- W3004651812 title "Role of TRPC6 on Single Cell Mechanics in Mouse Cardiomyocytes" @default.
- W3004651812 doi "https://doi.org/10.1016/j.bpj.2019.11.2345" @default.
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