Lipopolysaccharide (LPS) triggers an inflammatory response, causing impairment of cardiomyocyte Ca2+ and Na + regulation. This study aimed to determine whether piscidin-1 (PCD-1), an antimicrobial peptide, improves intracellular Ca2+ and Na + regulation in LPS-challenged atrial cardiomyocytes. Rabbit atrial cardiomyocytes were enzymatically isolated from the left atria. Patch-clamp ionic current recording, intracellular Ca2+ 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 Ca2+ channel currents and larger Na+/Ca2+ 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 LPS-induced alterations in the ionic current were ameliorated by PCD-1 treatment. LPS-challenged cardiomyocytes displayed lowered Ca2+ transient amplitudes and decreased Ca2+ stores and greater Ca2+ leakage in the sarcoplasmic reticulum compared to the control. Exposure to PCD-1 attenuated LPS-induced alterations in Ca2+ regulation. The elevated reactive oxygen species levels observed in LPS-challenged myocytes were suppressed after PCD-1 treatment. The protein levels of NF-κB and IL-6 increased following LPS treatment. Decreased sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a protein levels were observed in LPS-challenged cardiomyocytes. PCD-1 modulates LPS-induced alterations in inflammatory and Ca2+ regulatory protein levels. Our results suggest that PCD-1 modulates LPS-induced alterations in intracellular Ca2+ and Na + homeostasis, reactive oxygen species production, and the NF-κB inflammatory pathway in atrial cardiomyocytes.
Keywords: Atrial fibrillation; Calcium and sodium regulation; Lipopolysaccharide; Piscidin-1.
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