Pharmacological evaluation of R(+)-pulegone on cardiac excitability: Role of potassium current blockage and control of action potential waveform
Gondim, Antonio Nei
Rodrigues Menezes-Filho, Jose Evaldo
Lins Vasconcelos, Carla Marina
Cruz, Jader Santos
Roman-Campos, Danilo [UNIFESP]
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Introduction: R(+)-pulegone is a ketone monoterpene and it is the main constituent of essential oils in several plants. Previous studies provided some evidence that R(+)-pulegone may act on isolated cardiac myocytes. in this study, we evaluated in extended detail, the pharmacological effects of R(+)-pulegone on cardiac tissue.Methods: Using in vivo measurements of rat cardiac electrocardiogram (ECG) and patch-clamp technique in isolated myocytes we determinate the influence of R(+)-pulegone on cardiac excitability.Results: R(+)-pulegone delayed action potential repolarization (APR) in a concentration-dependent manner (EC50 = 775.7 +/- 1.48, 325.0 +/- 1.30, 469.3 +/- 1.91 mu M at 10, 50 and 90% of APR respectively). in line with prolongation of APR R(+)-pulegone, in a concentration-dependent manner, blocked distinct potassium current components (transient outward potassium current (I-to), rapid delayed rectifier potassium current (I-kr), inactivating steady state potassium current (I-ss) and inward rectifier potassium current (I-K1)) (EC50 = 1441 +/- 1.04; 605.0 +/- 1.22, 818.7 +/- 1.22; 1753 +/- 1.09 mu M for I-to, I-Kr, I-ss and I-K1, respectively). the inhibition occurred in a fast and reversible way, without changing the steady-state activation curve, but instead shifting to the left the steady-state inactivation curve (V-1/2 from -56.92 +/- 0.35 to 67.52 +/- 0.19 mV). in vivo infusion of 100 mg/kg R(+)-pulegone prolonged the QTc (similar to 40%) and PR (similar to 62%) interval along with reducing the heart rate by similar to 26%.Conclusion: Taken together, R(+)-pulegone prolongs the APR by inhibiting several cardiomyocyte current components in a concentration-dependent manner. This occurs through a direct block by R(+)pulegone of the channel pore, followed by a left shift on the steady state inactivation curve. Finally, R(+)-pulegone induced changes in some aspects of the ECG profile, which are in agreement with its effects on potassium channels of isolated cardiomyocytes. (C) 2014 Elsevier GmbH. All rights reserved.
CitationPhytomedicine. Jena: Elsevier Gmbh, Urban & Fischer Verlag, v. 21, n. 10, p. 1146-1153, 2014.
SponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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