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Updated: Aug 2, 2026
Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes
Published on: March 12, 2013
Inhibition of K+ currents by homocysteine in rat ventricular myocytes
1Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA.
Insights
High homocysteine levels impair heart repolarization by inhibiting the transient outward potassium current (I(to)) in heart cells. This finding suggests a direct link between homocysteine and potential cardiac arrhythmias.
Area of Science:
- Cardiovascular Physiology
- Electrophysiology
- Biochemistry
Background:
- Elevated homocysteine is linked to cardiovascular disease.
- The direct impact of homocysteine on heart electrophysiology remains unclear.
- Understanding these effects is crucial for assessing cardiac risk.
Purpose of the Study:
- To investigate the direct effects of homocysteine on cardiac electrophysiologic properties.
- To determine how homocysteine influences ion currents in heart cells.
Main Methods:
- Utilized whole-cell voltage-clamp recordings in isolated rat ventricular myocytes.
- Analyzed the transient outward potassium current (I(to)), a key repolarizing current.
- Examined the effects of homocysteine, homocystine, and homocysteine thiolactone.
Main Results:
- Homocysteine (500 microM) significantly decreased I(to) density by approximately 47%.
- Homocystine (500 microM) reduced I(to) density by approximately 40%.
- Inhibition was frequency- and voltage-dependent; thiolactone had no effect.
Conclusions:
- Homocysteine and homocystine directly inhibit I(to) channels in ventricular myocytes.
- Inhibition involves the thiol or disulfide moieties of these compounds.
- High levels may cause abnormal repolarization and contribute to arrhythmias.
Introduction:
Clinical evidence suggests that increased blood levels of homocysteine may be an independent risk factor for the development of cardiovascular disease, but the functional effects of this sulfhydryl amino acid on the myocardium are poorly understood. The present study was conducted to determine the direct effects of homocysteine on the electrophysiologic properties of the heart.
Methods And Results:
Whole-cell voltage-clamp recordings were made in ventricular myocytes isolated from normal rat hearts to analyze the Ca2+-independent, transient outward K+ current (I(to)), a major repolarizing current in these cells. Maximum I(to) density (measured at +60 mV) was decreased approximately 47% from baseline in the presence of 500 microM homocysteine (P < 0.05), but the amount of block varied in a frequency- and voltage-dependent manner. Decreased I(to) density was not accompanied by significant changes in voltage- or time-dependent properties of the current, nor was it affected by pretreating myocytes with the protein kinase inhibitor staurosporine. Because a portion of total extracellular homocysteine is oxidized, we examined the response to homocystine, the oxidized form of homocysteine. In myocytes superfused with 500 microM homocystine, maximum I(to) density was decreased by approximately 40% from baseline (P < 0.05). In contrast, the thiolactone form of homocysteine did not alter I(to) amplitude.
Conclusion:
These data suggest that homocysteine and its oxidized form homocystine acutely inhibit I(to) channels in ventricular myocytes by mechanisms involving the free thiol or disulfide moieties of these compounds. High homocysteine or homocystine levels may contribute to abnormal repolarization and arrhythmogenic conditions in the intact heart.
