Expressing a dominant-negative transient receptor potential canonical 6 (TRPC6) channel reduces the elevation of intracellular Ca²⁺ and sodium (Na⁺) concentrations elicited by 1-oleoyl-2-acetyl-sn-glycerol. Exposure of quiescent flexor digitorum brevis muscle fibers isolated from wild-type, wild-type/dominant-negative TRPC6, RYR1-p.R163C, and RYR1-p.R163C/dominant-negative TRPC6 mice to 100 µM 1-oleoyl-2-acetyl-sn-glycerol induced an elevation of intracellular Ca²⁺ (A) and sodium concentration (B). Expression of dominant-negative TRPC6 reduced the effect of 1-oleoyl-2-acetyl-sn-glycerol on both intracellular Ca²⁺ (A) and sodium (B) concentrations in both wild-type and RYR1-p.R163C muscle fibers. The experimental conditions are indicated on the horizontal axes. For intracellular Ca²⁺ concentration measurements: 5 mice per genotype, wild-type, 25 cells; wild-type dominant-negative TRPC6, 20 cells; RYR1-p.R163C 20 cells; RYR1-p.R163C/dominant-negative, n = 21 for intracellular Ca²⁺ concentration measurements. For intracellular sodium concentration measurements: 3 mice per genotype. Wild-type, 15 cells; wild-type dominant-negative TRPC6, 17 cells; RYR1-p.R163C, 18 cells; RYR1-p.R163C/dominant-negative TRPC6, 15 cells. The values are expressed as means ± SD for each condition. Statistical analysis was done using a one-way ANOVA with Tukey’s posttest. *P ≤ 0.05.