Hypercholesterolemia in the metabolic syndrome increases the functional expression of TRP channels in coronary myocytes from Ossabaw miniature swine

Activation of Ca 2+ ‐permeable transient receptor potential (TRP) channels contributes to smooth muscle proliferation. Sarcoplasmic reticulum (SR) Ca 2+ store depletion causes TRP mediated Ca 2+ influx. We tested the hypothesis that Ossabaw pigs that manifest the metabolic syndrome when fed excess high fat/cholesterol diet have greater TRP channel‐mediated Ca 2+ influx. Pigs were fed the following diets for 28 weeks: controls (11% kcal from fat; C; N = 5), high fructose (20% of kcal; F; N = 3), and high fructose, fat (46% of kcal), and cholesterol (2% by weight; H; N = 3). Coronary atherosclerosis was similar between C and F whereas it was significantly higher in H. Freshly isolated coronary smooth muscle cells were loaded with fura‐2 to measure intracellular Ca 2+ . Influx of Ca 2+ through TRP channels was determined by analyzing the Mn 2+ ‐induced quench of fura‐2 fluorescence at the Ca 2+ ‐insensitive wavelength of 360 nm upon SR Ca 2+ store depletion with caffeine and cyclopiazonic acid in a Ca 2+ ‐free solution. TRP channel activation was verified by blockade of Mn 2+ influx with Gd 3+ (10 μM), but not the voltage‐gated Ca 2+ channel antagonist nifedipine (10 μM). The rate of Mn 2+ influx was significantly higher in cells from H (−2.82 ± 0.36) compared to C (−0.89 ± 0.11) and F (−0.82± 0.46). In conclusion, hyperlipidemia increases TRP channel‐mediated Ca 2+ influx in coronary smooth muscle cells associated with atherosclerosis.