Mechanical and electrophysiological studies on the positive inotropic effect of 2‐phenyl‐4‐oxo‐hydroquinoline in rat cardiac tissues

Su, Ming Jai; Chang, Gwo‐Jyh; Kuo, Sheng Chu

doi:10.1111/j.1476-5381.1993.tb13810.x

Cited by 10 publications

(5 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The class III antiarrhythmic agents exert their antiarrhythmic effects by suppressing the K outward currents to prolong the action potential duration and thereby increase the refractoriness of the conduction system (Singh & Nademanee, 1985;Hondeghem & Katzung, 1987;Imaizumi & Giles, 1987;Dukes et al, 1990;Kurachi et al, 1990;Su et al, 1990;1993;Gwilt et al, 1991). Our results showed that N-allylsecovoldine could suppress the IKI and the Ito, which consequently prolonged the action potential duration and increased further the refractoriness of the myocardium.…”

Section: Modification Of the Electrophysiological Properties Of The Cmentioning

confidence: 99%

The electrophysiological effects of antiarrhythmic potential of a secoaporphine, N‐allylsecoboldine

Lee

et al. 1994

British J Pharmacology

View full text Add to dashboard Cite

1 A satisfactory antiarrhythmic potential of N-allylsecoboldine, a synthetic derivative of secoaporphine, has been documented. Its effects on the ionic currents of cardiac myocytes and the influence on the electrophysiological properties of the conduction system in Langendorff perfused hearts were investigated. 2 Ionic currents were studied by voltage clamp in the whole cell configuration. N-allylsecoboldine blocked the Na channel with a leftward-shift of its half voltage-dependent inactivation and a slower rate of recovery from the inactivation state. Similarly, calcium inward currents were inhibited but to a much smaller extent. 3 N-allylsecoboldine inhibited the 4-AP-sensitive transient outward K current. Currents through the K, channels were also reduced. 4 As compared with quinidine, N-allylsecoboldine caused a comparable degree of block on Na and K, currents but blocked to a lesser extent the Ca and I,. currents. 5 In the perfused whole-heart model, N-allylsecoboldine caused a dose-dependent prolongation in sinoatrial, atrioventricular and His-Purkinje system conduction intervals and prolonged the effective refractory periods of the atrium, AV node, His-Purkinje system and ventricle. However, the basic cycle length was not significantly affected. As compared to quinidine, N-allylsecoboldine exerted less pronounced effects on both the basic cycle length and the atrial and AV nodal refractory periods. 6 We conclude that N-allylsecoboldine predominantly blocks Na and K, channels and in similar concentrations partly blocks Ca channels and I,. These effects result in a modification of the electrophysiological properties of the conduction system which provides a satisfactory therapeutic potential for the treatment of cardiac arrhythmias.

show abstract

Section: Modification Of the Electrophysiological Properties Of The Cmentioning

confidence: 99%

The electrophysiological effects of antiarrhythmic potential of a secoaporphine, N‐allylsecoboldine

Lee

et al. 1994

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Among them, many alkaloids were found to have vasorelaxing [12,38,39] or antiarrhythmic activities [23, 40-42, 44, 48]. Consistent with their antiarrhythmic activities, electrophysiological studies revealed that these agents block cardiac Na + channels [35,36,45] and prolong the duration of action potential by inhibition of potassium outward currents [18,33,35,36,43].…”

Section: Introductionmentioning

confidence: 93%

Ionic Mechanisms for the Antiarrhythmic Action of Cinnamophilin in Rat Heart

Chen

et al. 1999

J Biomed Sci

View full text Add to dashboard Cite

We investigated the electrophysiological effect and antiarrhythmic potential of cinnamophilin (Cinn), a thromboxane A₂ antagonist isolated from Cinnamomum philippinense, on rat cardiac tissues. Action potential and ionic currents in single rat ventricular cells were examined by current clamp or voltage clamp in a whole-cell configuration. In 9 episodes of ischemia-reperfusion arrhythmia, 10 μM Cinn converted 6 of them to normal sinus rhythm. Cinn suppressed the maximal rate of rise of the action potential upstroke (V_max) and prolonged the action potential duration at 50% repolarization (APD₅₀). Voltage clamp study showed that the suppression of V_max by Cinn was associated with an inhibition of sodium inward current (I_Na, IC₅₀ = 10.0 ± 0.4 μM). At 30 μM, V_1/2 for the steady-state inactivation curve of I_Na was shifted from –84.1 ± 0.2 to –93.0 ± 0.5 mV. Cinn also reduced calcium inward current (I_Ca) dose-dependently with an IC₅₀ value of 9.5 ± 0.3 μM. Cinn (10 μM) reduced the I_Ca with a negative shift of V_1/2 for the steady-state inactivation curve of I_Ca from –32.2 ± 0.3 to –50.7 ± 0.4 mV. The prolongation of APD₅₀ was associated with an inhibition of the integral of potassium outward current with IC₅₀ values between 4.8 and 7.1 μM. At 10 μM, Cinn reduced I_Na without a negative shift of its voltage-dependent steady-state inactivation curves. The inhibition of transient outward current (I_to) by Cinn (3–30 μM) was associated with an acceleration of its time constant of inactivation and negative shift of its potential-dependent steady-state inactivation curves. The equilibrium dissociation constant (K_d) of Cinn to inhibit open state I_to channels, as calculated from the time constant of developing block, was 18.3 μM. The time constant of recovery of I_to from inactivation state was unaffected by Cinn. The rate constant for the relief from the depolarization-dependent block of I_to was calculated to be 23.9 ms. As compared with its effect on I_to, Cinn exerted about half the potency to block I_Na and I_Ca. These results indicate that the inhibition of I_Na, I_Ca and I_to may contribute to the antiarrhythmic activity of Cinn against ischemia-reperfusion arrhythmia.

show abstract

“…The leftward-shift of the potential-dependent steadystate inactivation curve of Ito by JKL1073A is similar to previous observations with dicentrine (Su et al, 1994b), but differs from clofilium (Castle, 1990b), propafenone (Duan et al, 1993), bupivacaine (Castle, 1990a), 2-phenyl-4-oxo-hydro- Figure 8a from the total current. quinoline (Su et al, 1993) and quinidine (Clark et al, 1995). A biphasic inhibition of It.…”

Section: Mechanism Of the Blocking Action Of Jkl1073a And Comparison mentioning

confidence: 99%

“…Rat single cells were isolated by procedures previously described (Mitra & Morad, 1985;Su et al, 1993). Briefly, the hearts were excised from rats and retrogradely perfused in a Langendorff apparatus with Ca2+-free HEPES-buffered Tyrode solution.…”

Section: Isolation Of Rat Atrial Myocytesmentioning

confidence: 99%

Mechanical and electrophysiological effects of 8‐oxoberberine (JKL1073A) on atrial tissue

Chi¹,

Chu²,

Lee³

et al. 1996

British J Pharmacology

View full text Add to dashboard Cite

1 The effects of 8-oxoberberine (JKL1073A) on contractions and electrophysiological characteristics of atrial tissues were examined.2 In driven left atria of the rat JKL1073A (10-100 gM) increased twitch tension dose-dependently. In spontaneously beating right atria, JKLI073A increased twitch tension but decreased beating rate slightly. 3 The positive inotropic and the negative chronotropic effect of 30 gM JKLI073A was not affected by prazosin (1 gM), propranolol (1 gM) and 3-isobutyl-1-methyl-xanthine (10 Mm) but significantly suppressed by 4-aminopyridine (2 mM 4-AP). 4 Current-clamp study revealed that JKL1073A prolonged rat atrial action potential duration (APD). This prolongation of APD by JKL1073A was decreased by pretreating the cells with 2 mM 4-AP.Voltage-clamp study showed that JKL1073A inhibited the integral of the transient outward current (It.)

show abstract

Mechanical and electrophysiological studies on the positive inotropic effect of 2‐phenyl‐4‐oxo‐hydroquinoline in rat cardiac tissues

Cited by 10 publications

References 31 publications

The electrophysiological effects of antiarrhythmic potential of a secoaporphine, N‐allylsecoboldine

The electrophysiological effects of antiarrhythmic potential of a secoaporphine, N‐allylsecoboldine

Ionic Mechanisms for the Antiarrhythmic Action of Cinnamophilin in Rat Heart

Mechanical and electrophysiological effects of 8‐oxoberberine (JKL1073A) on atrial tissue

Contact Info

Product

Resources

About