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 Ca2+ regulation and by impairing pacemaker "funny" current, If. We now explore further cellular mechanisms whereby LPS inhibits excitability in HL-1 cells. LPS (1 jxg/ml) derived from Salmonella enteritidis decreased rate of firing of spontaneous action potentials in HL-1 cells, and it increased their pacemaker potential durations and decreased their rates of depolarization, all measured by whole cell current clamp. LPS also increased action potential durations and decreased their amplitude in cells paced at 1 Hz with 0.1 nA, and 20 min were necessary for maximal effect. LPS decreased the amplitude of a rapidly inactivating inward current attributed to Na+ and of an outward current attributed to K+; both were measured by whole cell voltage clamp. The K+ currents displayed a resurgent outward tail current, which is characteristic of the rapid delayed-rectifier K+ current, Ikr. LPS accordingly reduced outward currents measured with pipette Cs+ substituted for K+ to isolate Ikr. E-4031 (1 (xM) markedly inhibited Ikr 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 Ikr and decreases their rate of firing by inhibition of Ina. 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.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-17364 |
| Date | 15 October 2012 |
| Creators | Wondergem, Robert, Graves, Bridget M., Li, Chuanfu, Williams, David L. |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | ETSU Faculty Works |
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