Korean J Physiol Pharmacol.  2010 Jun;14(3):119-125. 10.4196/kjpp.2010.14.3.119.

A Carbohydrate Fraction, AIP1, from Artemisia Iwayomogi Reduces the Action Potential Duration by Activation of Rapidly Activating Delayed Rectifier K+ Channels in Rabbit Ventricular Myocytes

• Park WS
• Son YK
• Ko EA
• Choi SW
• Kim N
• Choi TH
• Youn HJ
• Jo SH
• Hong DH
• Han J

• KMID: 2285391
• DOI: http://doi.org/10.4196/kjpp.2010.14.3.119

Abstract

We investigated the effects of a hot-water extract of Artemisia iwayomogi, a plant belonging to family Compositae, on cardiac ventricular delayed rectifier K+ current (I(K)) using the patch clamp technique. The carbohydrate fraction AIP1 dose-dependently increased the heart rate with an apparent EC(50) value of 56.1+/-5.5 microgram/ml. Application of AIP1 reduced the action potential duration (APD) in concentration-dependent fashion by activating I(K) without significantly altering the resting membrane potential (IC(50) value of APD(50): 54.80+/-2.24, IC(50) value of APD(90): 57.45+/-3.47 microgram/ml). Based on the results, all experiments were performed with 50 microgram/ml of AIP1. Pre-treatment with the rapidly activating delayed rectifier K+ current (I(Kr)) inhibitor, E-4031 prolonged APD. However, additional application of AIP1 did not reduce APD. The inhibition of slowly activating delayed rectifier K+ current (I(Ks)) by chromanol 293B did not change the effect of AIP1. AIP1 did not significantly affect coronary arterial tone or ion channels, even at the highest concentration of AIP1. In summary, AIP1 reduces APD by activating I(Kr) but not I(Ks). These results suggest that the natural product AIP1 may provide an adjunctive therapy of long QT syndrome.

Keyword

Artemisia iwayomogi; Delayed rectifier K+ current; Long QT syndrome; Ventricular myocyte

MeSH Terms

Action Potentials
Artemisia
Asteraceae
Chromans
Diphosphonates
Heart Rate
Humans
Ion Channels
Long QT Syndrome
Membrane Potentials
Muscle Cells
Piperidines
Plants
Pyridines
Sulfonamides
Chromans
Diphosphonates
Ion Channels
Piperidines
Pyridines
Sulfonamides

Figure

• 

  Fig. 1. Effect of AIP1 on the heart rate and action potentials of ventricular myocytes. (A) Does-dependent effect of AIP1 on the heart rate (All n=4 hearts). (B) Dose-dependent effect of AIP1 on APD. Superimposed traces of APs obtained using the patch-clamp technique under control conditions and in various concentrations of AIP1 with an apparent IC50 value of APD50 and APD90 (n=4 cells). (C) Representative traces of APs under control conditions in the presence of 50 μg/ml AIP1. (D, E) Summary of the APD50 and APD90 as shown in (C). APD50 and APD90 mean the time required for repolarization to 50% and to 90% of basal membrane potential, respectively. ∗p<0.05 (n=6 cells).

• 

  Fig. 2. AIP1 increased IK in ventricular cardiomyocyte. (A, B) Whole-cell current of ventricular cardiomyocytes under control conditions (A) and in the presence of 50 μg/ml AIP1 (B). Panel (a) was original recording traces and panel (b) was magnified traces of the panel (a). (C) Summary of whole-cell I-V relationship under control conditions (❍) and in the presence of 50 μg/ml AIP1 (). (D) Statistical summary of IK at +40 mV. ∗p<0.05 (n=5 cells).

• 

  Fig. 3. The effect of AIP1 on ICa in ventricular cardiomyocyte. (A) ICa in ventricular cardiomyocytes under control conditions and in the presence of 50 μg/ml AIP1. ICa was confirmed using the ICa inhibitor, nifedipine (10 μM). (B) Statistical summary of ICa at 0 mV. NS, not significant (Control vs AIP1, n=4 cells). ∗p<0.05 (Control vs nifedipine, n=4 cells). #p<0.05 (AIP1 vs nifedipine, n=4 cells).

• 

  Fig. 4. Effects of AIP1 on IKr and IKs. (A) Representative traces of action potentials obtained under control conditions, in the presence of 10 μM E-4031, and with additional application of 50 μg/ml AIP1. (B) Summary of APD50 as shown in (A). ∗p<0.05 (Control vs E-4031 + AIP1, n=6 cells). NS, not significant (E-4031 vs E-4031 + AIP1, n=6 cells). (C) The traces of action potentials obtained under control conditions, in the presence of 20 μM chromanol 293B, and with additional application of 50 μg/ml AIP1. (D) Summary of APD50 as shown in (C). ∗p<0.05 (Control vs chromanol 293B+AIP1, n=4 cells). #p<0.05 (chromanol 293B vs chromanol 293B + AIP1, n=4 cells).

• 

  Fig. 5. AIP1 did not affect coronary vascular tone or ion channels. (A) Representative traces showing the effect of various concentrations of AIP1 on vascular tone in coronary arteries. At the end of each experiment, 60 mM high K+ solution was applied to test the effectiveness of arteries (n=4 tissues). (B) Voltage-dependent K+ currents recorded using the ramp-pulse protocol (from –80 to + 60 mV for 280 ms) under control conditions (black line, n=5 cells) and in the presence of 50 μg/ml AIP1 (blue line, n=5 cells). (C) I-V relationship of voltage-dependent K+ currents obtained by step voltages (from –80 and +60 mV in steps of 10 mV) under control conditions (❍, n=5 cells) and in the presence of 50 μg/ml AIP1 (, n=5 cells). (D) vascular Ca2+ currents obtained by one step voltage (– 60 mV to 0 mV) under control condition and in the presence of 50 μg/ml AIP1. (E) Statistical summary of ICa at 0 mV. NS, not significant (Control vs AIP1, n=3 cells).

Reference

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