Effect of ethanol on action potential and ionic membrane currents in rat ventricular myocytes
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
20618172
DOI
10.1111/j.1748-1716.2010.02162.x
PII: APS2162
Knihovny.cz E-resources
- MeSH
- Action Potentials drug effects MeSH
- Potassium metabolism MeSH
- Ethanol pharmacology MeSH
- Ion Channel Gating drug effects MeSH
- Ion Channels metabolism MeSH
- Myocytes, Cardiac * cytology drug effects MeSH
- Rats MeSH
- Central Nervous System Depressants pharmacology MeSH
- Membrane Potentials drug effects MeSH
- Patch-Clamp Techniques MeSH
- Rats, Wistar MeSH
- Solvents MeSH
- Sodium metabolism MeSH
- Heart Ventricles cytology MeSH
- Calcium metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Potassium MeSH
- Ethanol MeSH
- Ion Channels MeSH
- Central Nervous System Depressants MeSH
- Solvents MeSH
- Sodium MeSH
- Calcium MeSH
AIM: Even though alcohol intoxication is often linked to arrhythmias, data describing ethanol effect on cardiac ionic channels are rare. In addition, ethanol is used as a solvent of hydrophobic compounds in experimental studies. We investigated changes of the action potential (AP) configuration and main ionic membrane currents in rat cardiomyocytes under 20-1500 m(M) ethanol. METHODS: Experiments were performed on enzymatically isolated rat right ventricular myocytes using the whole cell patch-clamp technique at room temperature. RESULTS: Ethanol reversibly decelerated the upstroke velocity and decreased AP amplitude and duration at 0.2 and 3 Hz. The fast sodium current I(Na) , l-type calcium current I(Ca) and transient outward potassium current I(to) were reversibly inhibited in a concentration-dependent manner (50% inhibition at 446 ± 12, 553 ± 49 and 1954 ± 234 m(M), respectively, with corresponding Hill coefficients 3.1 ± 0.3, 1.1 ± 0.2 and 0.9 ± 0.1). Suppression of I(Na) and I(Ca) magnitude was slightly voltage dependent. The effect on I(Ca) and I(to) was manifested mainly as an acceleration of their apparent inactivations with a decreased slow and fast time constant respectively. As a consequence of marked differences in n(H) , sensitivity of the currents to ethanol at 10% inhibition decreases in the following order: I(Ca) (75 mm, 3.5‰), I(to) (170 m(M), 7.8‰) and I(Na) (220 m(M), 10.1‰). CONCLUSION: Our results suggest a slight inhibition of all the currents at ethanol concentrations relevant to deep alcohol intoxication. The concentration dependence measured over a wide range may serve as a guideline when using ethanol as a solvent.
References provided by Crossref.org
Inward rectifying potassium currents resolved into components: modeling of complex drug actions
