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Acetate transiently inhibits myocardial contraction by increasing mitochondrial calcium uptake.

Schooley JF, Namboodiri AM, Cox RT, Bünger R, Flagg TP - BMC Physiol. (2014)

Bottom Line: Acute exposure of myocytes to 10 mM sodium acetate caused a marked, but transient, decrease in systolic sarcomere shortening (1.49 ± 0.20% vs. 5.58 ± 0.49% in control), accompanied by a significant increase in diastolic sarcomere length (1.81 ± 0.01 μm vs. 1.77 ± 0.01 μm in control), with a near linear dose response in the 1-10 mM range.Unlike palmitate, acetate caused no change in action potential duration; however, acetate markedly increased mitochondrial Ca(2+) uptake.Lehninger and others have previously demonstrated that the anions of weak aliphatic acids such as acetate stimulate Ca(2+) uptake in isolated mitochondria.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, Physiology, and Genetics, Uniformed Services University for the Health Sciences, 4301 Jones Bridge Road, Rm. C-2114, Bethesda, 20814, MD, USA. James.Schooley@usuhs.edu.

ABSTRACT

Background: There is a close relationship between cardiovascular disease and cardiac energy metabolism, and we have previously demonstrated that palmitate inhibits myocyte contraction by increasing Kv channel activity and decreasing the action potential duration. Glucose and long chain fatty acids are the major fuel sources supporting cardiac function; however, cardiac myocytes can utilize a variety of substrates for energy generation, and previous studies demonstrate the acetate is rapidly taken up and oxidized by the heart. In this study, we tested the effects of acetate on contractile function of isolated mouse ventricular myocytes.

Results: Acute exposure of myocytes to 10 mM sodium acetate caused a marked, but transient, decrease in systolic sarcomere shortening (1.49 ± 0.20% vs. 5.58 ± 0.49% in control), accompanied by a significant increase in diastolic sarcomere length (1.81 ± 0.01 μm vs. 1.77 ± 0.01 μm in control), with a near linear dose response in the 1-10 mM range. Unlike palmitate, acetate caused no change in action potential duration; however, acetate markedly increased mitochondrial Ca(2+) uptake. Moreover, pretreatment of cells with the mitochondrial Ca(2+) uptake blocker, Ru-360 (10 μM), markedly suppressed the effect of acetate on contraction.

Conclusions: Lehninger and others have previously demonstrated that the anions of weak aliphatic acids such as acetate stimulate Ca(2+) uptake in isolated mitochondria. Here we show that this effect of acetate appears to extend to isolated cardiac myocytes where it transiently modulates cell contraction.

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Related in: MedlinePlus

Acetate does not affect the action potential duration (APD90). (A) Representative action potentials recorded before (Control, gray line) and 2 minutes following acetate exposure (Acetate, black line). Action potentials were recorded in whole cell current clamp mode and were evoked suprathreshold current injections. Records are averaged traces from 25 consecutive action potentials. (B) Summary APD90 data from all (n = 7) experiments as in A. Acetate exposure did not affect the APD90 (24.5 ± 3.2 msec in acetate vs. 25.0 ± 3.5 msec in control).
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Fig3: Acetate does not affect the action potential duration (APD90). (A) Representative action potentials recorded before (Control, gray line) and 2 minutes following acetate exposure (Acetate, black line). Action potentials were recorded in whole cell current clamp mode and were evoked suprathreshold current injections. Records are averaged traces from 25 consecutive action potentials. (B) Summary APD90 data from all (n = 7) experiments as in A. Acetate exposure did not affect the APD90 (24.5 ± 3.2 msec in acetate vs. 25.0 ± 3.5 msec in control).

Mentions: We previously demonstrated that acute exposure to long chain fatty acids shortens the action potential duration principally by increasing outward voltage-dependent K+ currents encoded by Kv2.1 and Kv1.5, with no effect on IK1 [2]. Considering that short-chain fatty acids might have similar effects on cell excitability, we examined the effect of acetate on the action potential duration (APD90) (Figure 3). In contrast to results with palmitate, APD90 (24.5 ± 3.2 msec in control) was unaffected by acetate (25.0 ± 3.5 msec, p >0.05, paired t-test), suggesting that a different molecular mechanism underlies the inotropic effects of acetate.Figure 3


Acetate transiently inhibits myocardial contraction by increasing mitochondrial calcium uptake.

Schooley JF, Namboodiri AM, Cox RT, Bünger R, Flagg TP - BMC Physiol. (2014)

Acetate does not affect the action potential duration (APD90). (A) Representative action potentials recorded before (Control, gray line) and 2 minutes following acetate exposure (Acetate, black line). Action potentials were recorded in whole cell current clamp mode and were evoked suprathreshold current injections. Records are averaged traces from 25 consecutive action potentials. (B) Summary APD90 data from all (n = 7) experiments as in A. Acetate exposure did not affect the APD90 (24.5 ± 3.2 msec in acetate vs. 25.0 ± 3.5 msec in control).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4274725&req=5

Fig3: Acetate does not affect the action potential duration (APD90). (A) Representative action potentials recorded before (Control, gray line) and 2 minutes following acetate exposure (Acetate, black line). Action potentials were recorded in whole cell current clamp mode and were evoked suprathreshold current injections. Records are averaged traces from 25 consecutive action potentials. (B) Summary APD90 data from all (n = 7) experiments as in A. Acetate exposure did not affect the APD90 (24.5 ± 3.2 msec in acetate vs. 25.0 ± 3.5 msec in control).
Mentions: We previously demonstrated that acute exposure to long chain fatty acids shortens the action potential duration principally by increasing outward voltage-dependent K+ currents encoded by Kv2.1 and Kv1.5, with no effect on IK1 [2]. Considering that short-chain fatty acids might have similar effects on cell excitability, we examined the effect of acetate on the action potential duration (APD90) (Figure 3). In contrast to results with palmitate, APD90 (24.5 ± 3.2 msec in control) was unaffected by acetate (25.0 ± 3.5 msec, p >0.05, paired t-test), suggesting that a different molecular mechanism underlies the inotropic effects of acetate.Figure 3

Bottom Line: Acute exposure of myocytes to 10 mM sodium acetate caused a marked, but transient, decrease in systolic sarcomere shortening (1.49 ± 0.20% vs. 5.58 ± 0.49% in control), accompanied by a significant increase in diastolic sarcomere length (1.81 ± 0.01 μm vs. 1.77 ± 0.01 μm in control), with a near linear dose response in the 1-10 mM range.Unlike palmitate, acetate caused no change in action potential duration; however, acetate markedly increased mitochondrial Ca(2+) uptake.Lehninger and others have previously demonstrated that the anions of weak aliphatic acids such as acetate stimulate Ca(2+) uptake in isolated mitochondria.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, Physiology, and Genetics, Uniformed Services University for the Health Sciences, 4301 Jones Bridge Road, Rm. C-2114, Bethesda, 20814, MD, USA. James.Schooley@usuhs.edu.

ABSTRACT

Background: There is a close relationship between cardiovascular disease and cardiac energy metabolism, and we have previously demonstrated that palmitate inhibits myocyte contraction by increasing Kv channel activity and decreasing the action potential duration. Glucose and long chain fatty acids are the major fuel sources supporting cardiac function; however, cardiac myocytes can utilize a variety of substrates for energy generation, and previous studies demonstrate the acetate is rapidly taken up and oxidized by the heart. In this study, we tested the effects of acetate on contractile function of isolated mouse ventricular myocytes.

Results: Acute exposure of myocytes to 10 mM sodium acetate caused a marked, but transient, decrease in systolic sarcomere shortening (1.49 ± 0.20% vs. 5.58 ± 0.49% in control), accompanied by a significant increase in diastolic sarcomere length (1.81 ± 0.01 μm vs. 1.77 ± 0.01 μm in control), with a near linear dose response in the 1-10 mM range. Unlike palmitate, acetate caused no change in action potential duration; however, acetate markedly increased mitochondrial Ca(2+) uptake. Moreover, pretreatment of cells with the mitochondrial Ca(2+) uptake blocker, Ru-360 (10 μM), markedly suppressed the effect of acetate on contraction.

Conclusions: Lehninger and others have previously demonstrated that the anions of weak aliphatic acids such as acetate stimulate Ca(2+) uptake in isolated mitochondria. Here we show that this effect of acetate appears to extend to isolated cardiac myocytes where it transiently modulates cell contraction.

Show MeSH
Related in: MedlinePlus