Piscidin-1 regulates lipopolysaccharide-induced intracellular calcium, sodium dysregulation, and oxidative stress in atrial cardiomyocytes

Lipopolysaccharide (LPS) triggers an inflammatory response, causing impairment of cardiomyocyte Ca 2 + and Na + regulation. This study aimed to determine whether piscidin-1 (PCD-1), an antimicrobial peptide, improves intracellular Ca 2 + and Na + regulation in LPS-challenged atrial cardiomyocytes. Rabbit atrial cardiomyocytes were enzymatically isolated from the left atria. Patch -clamp ionic current recording, intracellular Ca 2 + monitoring using Fluo-3, and detection of cytosolic reactive oxygen species production were conducted in control, LPS-challenged, and LPS + PCD-1-treated atrial cardiomyocytes. LPS-challenged cardiomyocytes showed shortened durations of action potential at their 50% and 90% repolarizations, which was reversed by PCD-1 treatment. LPS-challenged cardiomyocytes showed decreased L -type Ca 2 + channel currents and larger Na + / Ca 2 + exchange currents compared to controls. While LPS did not affect the sodium current, an enhanced late sodium current with increased cytosolic Na + levels was observed in LPS-challenged cardiomyocytes. These LPSinduced alterations in the ionic current were ameliorated by PCD-1 treatment. LPS-challenged cardiomyocytes displayed lowered Ca 2 + transient amplitudes and decreased Ca 2 + stores and greater Ca 2 + leakage in the sarcoplasmic reticulum compared to the control. Exposure to PCD-1 attenuated LPS-induced alterations in Ca 2 + regulation. The elevated reactive oxygen species levels observed in LPS-challenged myocytes were suppressed after PCD-1 treatment. The protein levels of NF- c B and IL -6 increased following LPS treatment. Decreased sarcoplasmic/endoplasmic reticulum Ca 2 + ATPase 2a protein levels were observed in LPS-challenged cardiomyocytes. PCD-1 modulates LPS-induced alterations in inflammatory and Ca 2 + regulatory protein levels. Our results suggest that PCD-1 modulates LPS-induced alterations in intracellular Ca 2 + and Na + homeostasis, reactive oxygen species production, and the NF- c B inflammatory pathway in atrial cardiomyocytes.