Free fatty acid effects on the atrial myocardium: Membrane ionic currents are remodeled by the disruption of T-tubular architecture

Ryan P. O'Connell, Hassan Musa, Mario San Martin Gomez, Uma Mahesh Avula, Todd J. Herron, Jerome Kalifa, Justus M.B. Anumonwo, Alena Talkachova

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Epicardial adiposity and plasma levels of free fatty acids (FFAs) are elevated in atrial fibrillation, heart failure and obesity, with potentially detrimental effects on myocardial function. As major components of epicardial fat, FFAs may be abnormally regulated, with a potential to detrimentally modulate electro-mechanical function. The cellular mechanisms underlying such effects of FFAs are unknown. Objective: To determine the mechanisms underlying electrophysiological effects of palmitic (PA), stearic (SA) and oleic (OA) FFAs on sheep atrial myocytes. Methods: We used electrophysiological techniques, numerical simulations, biochemistry and optical imaging to examine the effects of acutely (≤ 15 min), short-term (4-6 hour) or 24-hour application of individual FFAs (10 μM) on isolated ovine left atrial myocytes (LAMs). Results: Acute and short-term incubation in FFAs resulted in no differences in passive or active properties of isolated left atrial myocytes (LAMs). 24-hour application had differential effects depending on the FFA. PA did not affect cellular passive properties but shortened (p<0.05) action potential duration at 30% repolarization (APD30). APD50 and APD80 were unchanged. SA had no effect on resting membrane potential but reduced membrane capacitance by 15% (p<0.05), and abbreviated APD at all values measured (p<0.001). OA did not significantly affect passive or active properties of LAMs. Measurement of the major voltage-gated ion channels in SA treated LAMs showed a ∼60% reduction (p<0.01) of the L-type calcium current (ICa-L) and ∼30% reduction (p<0.05) in the transient outward potassium current (ITO). A human atrial cell model recapitulated SA effects on APD. Optical imaging showed that SA incubated for 24 hours altered t-tubular structure in isolated cells (p<0.0001). Conclusions: SA disrupts t-tubular architecture and remodels properties of membrane ionic currents in sheep atrial myocytes, with potential implications in arrhythmogenesis.

Original languageEnglish (US)
Article numbere0133052
JournalPloS one
Volume10
Issue number8
DOIs
StatePublished - Aug 14 2015

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myocardium
Nonesterified Fatty Acids
free fatty acids
Myocardium
myocytes
Muscle Cells
pamidronate
Membranes
Sheep
Optical Imaging
sheep
image analysis
Imaging techniques
Biochemistry
capacitance
cell structures
Adiposity
ion channels
adiposity
heart failure

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Free fatty acid effects on the atrial myocardium : Membrane ionic currents are remodeled by the disruption of T-tubular architecture. / O'Connell, Ryan P.; Musa, Hassan; Gomez, Mario San Martin; Avula, Uma Mahesh; Herron, Todd J.; Kalifa, Jerome; Anumonwo, Justus M.B.; Talkachova, Alena.

In: PloS one, Vol. 10, No. 8, e0133052, 14.08.2015.

Research output: Contribution to journalArticle

O'Connell, Ryan P. ; Musa, Hassan ; Gomez, Mario San Martin ; Avula, Uma Mahesh ; Herron, Todd J. ; Kalifa, Jerome ; Anumonwo, Justus M.B. ; Talkachova, Alena. / Free fatty acid effects on the atrial myocardium : Membrane ionic currents are remodeled by the disruption of T-tubular architecture. In: PloS one. 2015 ; Vol. 10, No. 8.
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abstract = "Background: Epicardial adiposity and plasma levels of free fatty acids (FFAs) are elevated in atrial fibrillation, heart failure and obesity, with potentially detrimental effects on myocardial function. As major components of epicardial fat, FFAs may be abnormally regulated, with a potential to detrimentally modulate electro-mechanical function. The cellular mechanisms underlying such effects of FFAs are unknown. Objective: To determine the mechanisms underlying electrophysiological effects of palmitic (PA), stearic (SA) and oleic (OA) FFAs on sheep atrial myocytes. Methods: We used electrophysiological techniques, numerical simulations, biochemistry and optical imaging to examine the effects of acutely (≤ 15 min), short-term (4-6 hour) or 24-hour application of individual FFAs (10 μM) on isolated ovine left atrial myocytes (LAMs). Results: Acute and short-term incubation in FFAs resulted in no differences in passive or active properties of isolated left atrial myocytes (LAMs). 24-hour application had differential effects depending on the FFA. PA did not affect cellular passive properties but shortened (p<0.05) action potential duration at 30{\%} repolarization (APD30). APD50 and APD80 were unchanged. SA had no effect on resting membrane potential but reduced membrane capacitance by 15{\%} (p<0.05), and abbreviated APD at all values measured (p<0.001). OA did not significantly affect passive or active properties of LAMs. Measurement of the major voltage-gated ion channels in SA treated LAMs showed a ∼60{\%} reduction (p<0.01) of the L-type calcium current (ICa-L) and ∼30{\%} reduction (p<0.05) in the transient outward potassium current (ITO). A human atrial cell model recapitulated SA effects on APD. Optical imaging showed that SA incubated for 24 hours altered t-tubular structure in isolated cells (p<0.0001). Conclusions: SA disrupts t-tubular architecture and remodels properties of membrane ionic currents in sheep atrial myocytes, with potential implications in arrhythmogenesis.",
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T1 - Free fatty acid effects on the atrial myocardium

T2 - Membrane ionic currents are remodeled by the disruption of T-tubular architecture

AU - O'Connell, Ryan P.

AU - Musa, Hassan

AU - Gomez, Mario San Martin

AU - Avula, Uma Mahesh

AU - Herron, Todd J.

AU - Kalifa, Jerome

AU - Anumonwo, Justus M.B.

AU - Talkachova, Alena

PY - 2015/8/14

Y1 - 2015/8/14

N2 - Background: Epicardial adiposity and plasma levels of free fatty acids (FFAs) are elevated in atrial fibrillation, heart failure and obesity, with potentially detrimental effects on myocardial function. As major components of epicardial fat, FFAs may be abnormally regulated, with a potential to detrimentally modulate electro-mechanical function. The cellular mechanisms underlying such effects of FFAs are unknown. Objective: To determine the mechanisms underlying electrophysiological effects of palmitic (PA), stearic (SA) and oleic (OA) FFAs on sheep atrial myocytes. Methods: We used electrophysiological techniques, numerical simulations, biochemistry and optical imaging to examine the effects of acutely (≤ 15 min), short-term (4-6 hour) or 24-hour application of individual FFAs (10 μM) on isolated ovine left atrial myocytes (LAMs). Results: Acute and short-term incubation in FFAs resulted in no differences in passive or active properties of isolated left atrial myocytes (LAMs). 24-hour application had differential effects depending on the FFA. PA did not affect cellular passive properties but shortened (p<0.05) action potential duration at 30% repolarization (APD30). APD50 and APD80 were unchanged. SA had no effect on resting membrane potential but reduced membrane capacitance by 15% (p<0.05), and abbreviated APD at all values measured (p<0.001). OA did not significantly affect passive or active properties of LAMs. Measurement of the major voltage-gated ion channels in SA treated LAMs showed a ∼60% reduction (p<0.01) of the L-type calcium current (ICa-L) and ∼30% reduction (p<0.05) in the transient outward potassium current (ITO). A human atrial cell model recapitulated SA effects on APD. Optical imaging showed that SA incubated for 24 hours altered t-tubular structure in isolated cells (p<0.0001). Conclusions: SA disrupts t-tubular architecture and remodels properties of membrane ionic currents in sheep atrial myocytes, with potential implications in arrhythmogenesis.

AB - Background: Epicardial adiposity and plasma levels of free fatty acids (FFAs) are elevated in atrial fibrillation, heart failure and obesity, with potentially detrimental effects on myocardial function. As major components of epicardial fat, FFAs may be abnormally regulated, with a potential to detrimentally modulate electro-mechanical function. The cellular mechanisms underlying such effects of FFAs are unknown. Objective: To determine the mechanisms underlying electrophysiological effects of palmitic (PA), stearic (SA) and oleic (OA) FFAs on sheep atrial myocytes. Methods: We used electrophysiological techniques, numerical simulations, biochemistry and optical imaging to examine the effects of acutely (≤ 15 min), short-term (4-6 hour) or 24-hour application of individual FFAs (10 μM) on isolated ovine left atrial myocytes (LAMs). Results: Acute and short-term incubation in FFAs resulted in no differences in passive or active properties of isolated left atrial myocytes (LAMs). 24-hour application had differential effects depending on the FFA. PA did not affect cellular passive properties but shortened (p<0.05) action potential duration at 30% repolarization (APD30). APD50 and APD80 were unchanged. SA had no effect on resting membrane potential but reduced membrane capacitance by 15% (p<0.05), and abbreviated APD at all values measured (p<0.001). OA did not significantly affect passive or active properties of LAMs. Measurement of the major voltage-gated ion channels in SA treated LAMs showed a ∼60% reduction (p<0.01) of the L-type calcium current (ICa-L) and ∼30% reduction (p<0.05) in the transient outward potassium current (ITO). A human atrial cell model recapitulated SA effects on APD. Optical imaging showed that SA incubated for 24 hours altered t-tubular structure in isolated cells (p<0.0001). Conclusions: SA disrupts t-tubular architecture and remodels properties of membrane ionic currents in sheep atrial myocytes, with potential implications in arrhythmogenesis.

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