PMID- 22895260
OWN - NLM
STAT- MEDLINE
DCOM- 20130104
LR  - 20211021
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 303
IP  - 8
DP  - 2012 Oct 15
TI  - Lipopolysaccharide prolongs action potential duration in HL-1 mouse 
      cardiomyocytes.
PG  - C825-33
LID - 10.1152/ajpcell.00173.2012 [doi]
AB  - 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 (1 mug/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, I(Kr). LPS 
      accordingly reduced outward currents measured with pipette Cs(+) substituted for 
      K(+) to isolate I(Kr). E-4031 (1 muM) 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.
FAU - Wondergem, Robert
AU  - Wondergem R
AD  - Department of Biomedical Science, James H. Quillen College of Medicine, East 
      Tennessee State University, Johnson City, Tennessee 37614-1708, USA. 
      wonderge@etsu.edu
FAU - Graves, Bridget M
AU  - Graves BM
FAU - Li, Chuanfu
AU  - Li C
FAU - Williams, David L
AU  - Williams DL
LA  - eng
GR  - R01 GM053522/GM/NIGMS NIH HHS/United States
GR  - R01 GM083016/GM/NIGMS NIH HHS/United States
GR  - GM-083016/GM/NIGMS NIH HHS/United States
GR  - GM-53522/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120815
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Delayed Rectifier Potassium Channels)
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - Action Potentials/drug effects/*physiology
MH  - Animals
MH  - Cell Line, Transformed
MH  - Delayed Rectifier Potassium Channels/physiology
MH  - Lipopolysaccharides/*pharmacology
MH  - Mice
MH  - Myocardial Contraction/drug effects/*physiology
MH  - Myocytes, Cardiac/cytology/drug effects/*physiology
MH  - Patch-Clamp Techniques/methods
MH  - Sepsis/physiopathology
PMC - PMC3469715
EDAT- 2012/08/17 06:00
MHDA- 2013/01/05 06:00
PMCR- 2013/10/15
CRDT- 2012/08/17 06:00
PHST- 2012/08/17 06:00 [entrez]
PHST- 2012/08/17 06:00 [pubmed]
PHST- 2013/01/05 06:00 [medline]
PHST- 2013/10/15 00:00 [pmc-release]
AID - ajpcell.00173.2012 [pii]
AID - C-00173-2012 [pii]
AID - 10.1152/ajpcell.00173.2012 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2012 Oct 15;303(8):C825-33. doi: 
      10.1152/ajpcell.00173.2012. Epub 2012 Aug 15.