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• W1993807839 abstract "The phosphoinositide 3-kinase (PI3K) inhibitor LY-294002 decreased steady-state contraction in neonatal rat ventricular myocytes (NRVM). To determine whether the effect on steady-state contraction could be due to decreased intracellular Ca(2+) content, Ca(2+) content was assessed with fluorescent plate reader analysis by using the caffeine-releasable Ca(2+) stores as an index of sarcoplasmic reticulum (SR) Ca(2+) content. Caffeine-releasable Ca(2+) content was diminished in a dose-dependent manner with LY-294002, suggesting that the decrease in steady-state contraction was due to diminished intracellular Ca(2+) content. Activation of the L-type Ca(2+) channel by BAY K 8644 was attenuated by LY-294002, suggesting the effect of LY-294002 is to reduce Ca(2+) influx at this channel. To investigate whether additional proteins involved in excitation-contraction (EC) coupling are likewise regulated by PI3K activity, the effects of compounds acting at sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a), the ryanodine receptor, and the Na/Ca exchanger (NCX) were compared with LY-294002. Inhibition of SERCA2a by thapsigargin increased basal Ca(2+) levels in contrast to LY-294002, indicating that SERCA2a activity is sustained in the presence of LY-294002. Ryanodine decreased SR Ca(2+) content. The additive effect with coadministration of LY-294002 could be attributed to a decrease in Ca(2+) influx at the L-type Ca(2+) channel. The NCX inhibitor Ni(2+) was used to investigate whether the decrease in intracellular Ca(2+) content with LY-294002 could be due to inhibition of the NCX reverse-mode activity. The minimal effect of LY-294002 with Ni(2+) suggests that the primary effect of LY-294002 on EC coupling occurs through inhibition of PI3K-mediated L-type Ca(2+) channel activity." @default.
• W1993807839 created "2016-06-24" @default.
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• W1993807839 date "2004-02-01" @default.
• W1993807839 modified "2023-10-15" @default.
• W1993807839 title "Phosphoinositide 3-kinase regulates excitation-contraction coupling in neonatal cardiomyocytes" @default.
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• W1993807839 doi "https://doi.org/10.1152/ajpheart.00546.2003" @default.
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