American journal of physiology. Cell physiology
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Am. J. Physiol., Cell Physiol. · Oct 2012
Lipopolysaccharide prolongs action potential duration in HL-1 mouse cardiomyocytes.
Sepsis has deleterious effects on cardiac function including reduced contractility. We have shown previously that lipopolysaccharides (LPS) directly affect HL-1 cardiac myocytes by inhibiting Ca(2+) regulation and by impairing pacemaker "funny" current, I(f). We now explore further cellular mechanisms whereby LPS inhibits excitability in HL-1 cells. ⋯ LPS accordingly reduced outward currents measured with pipette Cs(+) substituted for K(+) to isolate I(Kr). E-4031 (1 μM) markedly inhibited I(Kr) in HL-1 cells and also increased action potential duration; however, the direct effects of E-4031 occurred minutes faster than the slow effects of LPS. We conclude that LPS increases action potential duration in HL-1 mouse cardiomyocytes by inhibition of I(Kr) and decreases their rate of firing by inhibition of I(Na.) This protracted time course points toward an intermediary metabolic event, which either decreases available mouse ether-a-go-go (mERG) and Na(+) channels or potentiates their inactivation.