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Updated: Aug 8, 2026
Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013
Effect of thymol on calcium handling in mammalian ventricular myocardium
Norbert Szentandrássy1, Gyula Szigeti, Csaba Szegedi
1Department of Physiology, University Medical School of Debrecen, H-4012, Debrecen, P.O.Box 22, Hungary.
Insights
Thymol affects cardiac calcium handling, causing concentration-dependent negative inotropy by releasing and inhibiting calcium reuptake. Lower doses may sensitize contractile machinery, indicating complex cardiac effects.
Area of Science:
- Cardiovascular Pharmacology
- Molecular Cardiology
- Biophysics
Background:
- Thymol, a natural compound, has demonstrated various biological activities.
- Understanding its precise effects on cardiac function is crucial for potential therapeutic applications.
- Calcium handling by the sarcoplasmic reticulum is fundamental to cardiac contractility.
Purpose of the Study:
- To investigate the concentration-dependent effects of thymol on cardiac calcium handling.
- To elucidate the mechanisms underlying thymol's inotropic actions.
- To examine thymol's interaction with cardiac calcium release channels and pumps.
Main Methods:
- Experiments utilized Langendorff-perfused guinea pig hearts, canine ventricular trabeculae, and isolated canine sarcoplasmic reticular vesicles.
- Single ryanodine receptors were reconstituted into artificial lipid bilayers.
- Concentration-response relationships were determined for thymol's effects on contractility, calcium transients, calcium release, and calcium pump activity.
Main Results:
- Thymol induced a concentration-dependent negative inotropic effect in both canine and guinea pig preparations.
- Low thymol concentrations reduced intracellular calcium transients without affecting contractility, suggesting a calcium-sensitizing effect.
- Higher concentrations suppressed both calcium transients and contractility, mediated by increased calcium release and inhibited calcium pump activity in sarcoplasmic reticular vesicles.
Conclusions:
- The negative inotropic action of thymol is attributed to reduced sarcoplasmic reticulum calcium content, resulting from enhanced calcium release and impaired calcium reuptake.
- Thymol's interaction with ryanodine receptors leads to prolonged channel openings, increasing calcium release.
- The dual effects of thymol on calcium handling, including potential calcium sensitization at low concentrations, highlight its complex impact on cardiac contractility.
Abstract:
Concentration-dependent effects of thymol on calcium handling were studied in canine and guinea pig cardiac preparations (Langendorff-perfused guinea pig hearts, canine ventricular trabeculae, canine sarcoplasmic reticular vesicles and single ryanodine receptors). Thymol induced a concentration-dependent negative inotropic action in both canine and guinea pig preparations (EC(50) = 297 +/- 12 microM in dog). However, low concentrations of thymol reduced intracellular calcium transients in guinea pig hearts without decreasing contractility. At higher concentrations both calcium transients and contractions were suppressed. In canine sarcoplasmic reticular vesicles thymol induced rapid release of calcium (V(max) = 0.47 +/- 0.04 nmol s(-1), EC(50) = 258 +/- 21 microM, Hill coefficient = 3.0 +/- 0.54), and decreased the activity of the calcium pump (EC(50) = 253 +/- 4.7 microM, Hill coefficient = 1.62 +/- 0.05). Due to the less sharp concentration-dependence of the ATPase inhibition, this effect was significant from 50 microM, whereas the thymol-induced calcium release only from 100 microM. In single ryanodine receptors incorporated into artificial lipid bilayer thymol induced long lasting openings, having mean open times increased with 3 orders of magnitude, however, the specific conductance of the channel remained unaltered. This effect of thymol was not voltage-dependent and failed to prevent the binding of ryanodine. In conclusion, the negative inotropic action of thymol can be explained by reduction in calcium content of the sarcoplasmic reticulum due to the combination of the thymol-induced calcium release and inhibition of the calcium pump. The calcium-sensitizer effect, observed at lower thymol concentrations, indicates that thymol is likely to interact with the contractile machinery also.
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