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

Chi, Jo-Feng; Chu, Shu‐Hsun; Lee, Chih-Shone; Chou, Nai‐Kuan; Su, Ming‐Jai

doi:10.1111/j.1476-5381.1996.tb15431.x

Cited by 25 publications

(13 citation statements)

References 48 publications

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“…The positive inotropic and the negative chronotropic effects of 8-oxoberberine are not likely to be mediated by autonomic nervous system, since neither prazosin, propranolol, or atropine modified the effects of 8-oxoberberine. The cyclic AMP-dependent pathway is not likely to be involved, since 3-isobutyl-1-methyl-xanthine, an inhibitor of phosphodiesterase, also did not alter the cardiac effects of 8-oxoberberine (6). Patch-clamp study revealed that 8-oxoberberine prolonged the duration of rat atrial action potential; 4-aminopyridine, a blocker of voltage-gated K + channels, blunted this effect.…”

Section: Cardiac Effect Of Berberine Derivativesmentioning

confidence: 97%

“…The I to blocking potency of 8-oxoberberine was greater than that of dicentrine but similar to that of quinidine (42). In human or rat aorta 8-oxoberberine, like berberine, had no effect on inwardly rectifier K + channels (6). In human or rat ventricular myocytes 8-oxoberberine had quinidine-like effects.…”

Section: Cardiac Effect Of Berberine Derivativesmentioning

confidence: 99%

“…A striking electrophysiological action of berberine and its derivatives on cardiac myocytes is lengthening of action potential without affecting other action potential characteristics. This effect was observed in various species including rats (6), guinea pigs (46), rabbits (37), cats (40), dogs (37), and humans (6). Selective lengthening of action potential duration would increase Ca 2+ influx through the transmembrane Ca 2+ channels, elevate Ca 2+ mobilization from the sarcoplasmic reticulum and rise cytostolic free Ca 2+ concentration required for enhanced cardiac contractility.…”

Section: Pharmacology Inotropic Effectmentioning

confidence: 99%

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Cardiovascular Actions of Berberine

Lau

Yao

Chen

et al. 2001

Cardiovascular Drug Reviews

242

126

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Berberine, is an alkaloid from Hydrastis canadensis L., Chinese herb Huanglian, and many other plants. It is widely used in traditional Chinese medicine as an antimicrobial in the treatment of dysentery and infectious diarrhea. This manuscript describes cardiovascular effects of berberine and its derivatives, tetrahydroberberine and 8-oxoberberine. Berberine has positive inotropic, negative chronotropic, antiarrhythmic, and vasodilator properties. Both derivatives of berberine have antiarrhythmic activity. Some of cardiovascular effects of berberine and its derivatives are attributed to the blockade of K + channels (delayed rectifier and K ATP ) and stimulation of Na + -Ca 2+ exchanger. Berberine has been shown to prolong the duration of ventricular action potential. Its vasodilator activity has been attributed to multiple cellular mechanisms. The cardiovascular effects of berberine suggest its possible clinical usefulness in the treatment of arrhythmias and/or heart failure.

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Section: Cardiac Effect Of Berberine Derivativesmentioning

confidence: 97%

Section: Cardiac Effect Of Berberine Derivativesmentioning

confidence: 99%

Section: Pharmacology Inotropic Effectmentioning

confidence: 99%

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Cardiovascular Actions of Berberine

Lau

Yao

Chen

et al. 2001

Cardiovascular Drug Reviews

242

126

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“…This failure suggests that (+)-MK801 has a low affinity for Na + channels in the inactivated state. [ 16,32], bupivacaine [4], dicentrine [27], thaliporphine [26] and other alkaloids [5][6][7][8].…”

Section: Mode Of Channel Bloanding Actions Of (+)-Mk801mentioning

confidence: 99%

Positive inotropic action of NMDA receptor antagonist (+)-MK801 in rat heart

Wang

1999

J Biomed Sci

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(+)-MK801, a noncompetitive NMDA receptor antagonist, was reported to exhibit anticonvulsive and neuroprotective activities during the postischemic period. Intravenous administration of (+)-MK801 produced tachycardia in rats, but bradycardia in pigs. We examined the mechanical and electrophysiological effects of (+)-MK801 on rat cardiac tissues. (+)-MK801 dose-dependently increased (3-100 microM) twitch tension in rat atria and ventricular strips. The spontaneous beating rate in rat right atria, however, was dose-dependently decreased by (+)-MK801. The inotropic effect of (+)-MK801 was affected neither by alpha(1)-antagonist (1 microM prazosin) nor by beta(1)-adrenoceptor antagonist (3 microM atenolol), but significantly by a transient outward K(+) channel blocker (3 mM 4-aminopyridine). (+)-MK801 did not cause any significant change of intracellular cAMP content. Electrophysiological study in rat ventricular cells revealed that (+)-MK801 concentration-dependently prolonged the action potential duration with a concomitant decrease in the maximum rate of the action potential upstroke (V(max)) and an increase in the recovery time constant of V(max). Voltage clamp study showed that (+)-MK801 (3 microM) reduced inward Na(+) current (I(Na)), along with a slowing of its recovery from inactivation and a slight negative shift of its voltage-dependent steady-state inactivation curves. At a much higher concentration (30 microM), (+)-MK801 slightly reduced the amplitude of L-type calcium inward current (I(Ca)), although the voltage dependence of its steady-state inactivation was unaffected. For the potassium currents in rat ventricular cells, 3 microM of (+)-MK801 reduced the peak transient outward current (I(to)), steady-state outward current (I(ss)) and inward current through K(1) channels. The inhibition of I(to) was associated with a prominent negative shift in the voltage dependence of its steady-state inactivation curve. The outward current through K(1) channels was unaffected. These results indicate that (+)-MK801 may be a strong I(Na) and I(to) blocker with some I(Ca) blocking activity. The inhibition of I(to) and other K(+) efflux would prolong action potential duration, produce positive inotropic action and contribute to the negative chronotropic effect of (+)-MK801.

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“…In view of the leftward shift of the I to inactivation curve and the failure to accelerate I to decay, (+)-MK801 may bind preferentially to inactivated I to channels instead of the open-state I to channels. This mode of inhibition of I to by (+)-MK801 is different from that by quinidine [16,32], bupivacaine [4], dicentrine [27], thaliporphine [26] and other alkaloids [5][6][7][8].…”

Section: Mode Of Channel Blocking Actions Of (+)-Mk801mentioning

confidence: 99%

Positive Inotropic Action of NMDA Receptor Antagonist (+)-MK801 in Rat Heart

Wang¹,

Su²

1999

J Biomed Sci

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(+)-MK801, a noncompetitive NMDA receptor antagonist, was reported to exhibit anticonvulsive and neuroprotective activities during the postischemic period. Intravenous administration of (+)-MK801 produced tachycardia in rats, but bradycardia in pigs. We examined the mechanical and electrophysiological effects of (+)-MK801 on rat cardiac tissues. (+)-MK801 dose-dependently increased (3–100 μM) twitch tension in rat atria and ventricular strips. The spontaneous beating rate in rat right atria, however, was dose-dependently decreased by (+)-MK801. The inotropic effect of (+)-MK801 was affected neither by α₁-antagonist (1 μM prazosin) nor by β₁-adrenoceptor antagonist (3 μM atenolol), but significantly by a transient outward K⁺ channel blocker (3 mM 4-aminopyridine). (+)-MK801 did not cause any significant change of intracellular cAMP content. Electrophysiological study in rat ventricular cells revealed that (+)-MK801 concentration-dependently prolonged the action potential duration with a concomitant decrease in the maximum rate of the action potential upstroke (V_max) and an increase in the recovery time constant of V_max. Voltage clamp study showed that (+)-MK801 (3 μM) reduced inward Na⁺ current (I_Na), along with a slowing of its recovery from inactivation and a slight negative shift of its voltage-dependent steady-state inactivation curves. At a much higher concentration (30 μM), (+)-MK801 slightly reduced the amplitude of L-type calcium inward current (I_Ca), although the voltage dependence of its steady-state inactivation was unaffected. For the potassium currents in rat ventricular cells, 3 μM of (+)-MK801 reduced the peak transient outward current (I_to), steady-state outward current (I_ss) and inward current through K₁ channels. The inhibition of I_to was associated with a prominent negative shift in the voltage dependence of its steady-state inactivation curve. The outward current through K₁ channels was unaffected. These results indicate that (+)-MK801 may be a strong I_Na and I_to blocker with some I_Ca blocking activity. The inhibition of I_to and other K⁺ efflux would prolong action potential duration, produce positive inotropic action and contribute to the negative chronotropic effect of (+)-MK801.

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

Cited by 25 publications

References 48 publications

Cardiovascular Actions of Berberine

Cardiovascular Actions of Berberine

Positive inotropic action of NMDA receptor antagonist (+)-MK801 in rat heart

Positive Inotropic Action of NMDA Receptor Antagonist (+)-MK801 in Rat Heart

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

Cited by 25 publications

References 48 publications

Cardiovascular Actions of Berberine

Cardiovascular Actions of Berberine

Positive inotropic action of NMDA receptor antagonist (+)-MK801 in rat heart

Positive Inotropic Action of NMDA Receptor Antagonist (&plus;)-MK801 in Rat Heart

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Positive Inotropic Action of NMDA Receptor Antagonist (+)-MK801 in Rat Heart