Merck
  • Inicio
  • Resultados de la búsqueda
  • Pharmacological evaluation of R(+)-pulegone on cardiac excitability: role of potassium current blockage and control of action potential waveform.

Pharmacological evaluation of R(+)-pulegone on cardiac excitability: role of potassium current blockage and control of action potential waveform.

Phytomedicine : international journal of phytotherapy and phytopharmacology (2014-06-11)
Artur Santos-Miranda, Antonio Nei Gondim, Jose Evaldo Rodrigues Menezes-Filho, Carla Marina Lins Vasconcelos, Jader Santos Cruz, Danilo Roman-Campos
RESUMEN

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. 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. 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 μM 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 μM 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 (V1/2 from -56.92±0.35 to -67.52±0.19 mV). In vivo infusion of 100 mg/kg R(+)-pulegone prolonged the QTc (∼40%) and PR (∼62%) interval along with reducing the heart rate by ∼26%. Taken together, R(+)-pulegone prolongs the APR by inhibiting several cardiomyocyte K(+) 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.

MATERIALES
Referencia del producto
Marca
Descripción del producto

USP
Dimethyl sulfoxide, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Dimethyl sulfoxide, ReagentPlus®, ≥99.5%
Sigma-Aldrich
Dimethyl sulfoxide, puriss. p.a., dried, ≤0.02% water
Sigma-Aldrich
Dimethyl sulfoxide, ACS reagent, ≥99.9%
Sigma-Aldrich
Dimethyl sulfoxide, puriss. p.a., ACS reagent, ≥99.9% (GC)
Dimethyl sulfoxide, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Dimethyl sulfoxide, suitable for HPLC, ≥99.7%
Supelco
Dimethyl sulfoxide, for inorganic trace analysis, ≥99.99995% (metals basis)
Sigma-Aldrich
Dimethyl sulfoxide solution, 50 wt. % in H2O
Sigma-Aldrich
Sodium bicarbonate-12C, 99.9 atom % 12C
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
8-Octanoyloxypyrene-1,3,6-trisulfonic acid trisodium salt, suitable for fluorescence, ≥90% (HPCE)
Sigma-Aldrich
Sodium hydroxide-16O solution, 20 wt. % in H216O, 99.9 atom % 16O
Sigma-Aldrich
Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
Sigma-Aldrich
Dimethyl sulfoxide, PCR Reagent
Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Supelco
Dimethyl sulfoxide, analytical standard
Sigma-Aldrich
Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
Sigma-Aldrich
Sodium bicarbonate, BioXtra, 99.5-100.5%
Sigma-Aldrich
Sodium bicarbonate, Hybri-Max, powder, suitable for hybridoma, ≥99.5%
Sigma-Aldrich
Sodium bicarbonate, powder, BioReagent, for molecular biology, suitable for cell culture, suitable for insect cell culture
Sigma-Aldrich
Sodium hydroxide solution, 1.0 N, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid, ≥97.0%
Sigma-Aldrich
HEPES, ≥99.5% (titration)
Sigma-Aldrich
HEPES, BioXtra, pH 5.0-6.5 (1 M in H2O), ≥99.5% (titration)
Sigma-Aldrich
HEPES, BioXtra, suitable for mouse embryo cell culture, ≥99.5% (titration)
Sigma-Aldrich
HEPES, BioPerformance Certified, ≥99.5% (titration), suitable for cell culture