These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Effects of 8-oxoberberine on sodium current in rat ventricular and human atrial myocytes.
    Author: Chi JF, Chu SH, Lee CS, Su MJ.
    Journal: Can J Cardiol; 1997 Nov; 13(11):1103-10. PubMed ID: 9413244.
    Abstract:
    8-Oxoberberine (JKL1073A), a derivative of berberine, has been reported to exert positive inotropic action and antiarrhythmic activity, much like a class III antiarrhythmic agent. In addition to prolongation of cardiac action potential duration, JKL1073A also decreases the maximal rate of action potential upstroke. To characterize the mode of inhibition of action potential upstroke, the effects of JKL1073A on the sodium inward current (INa) of rat and human cardiac myocytes were examined by voltage clamp in a whole cell configuration. In rat ventricular myocytes, JKL1073A and quinidine inhibited INa with an average 50% inhibitory concentration (IC50) of 3.3 +/- 0.2 microM (n = 9) and 2.1 +/- 0.1 microM (n = 6), respectively. Voltage-dependent steady state inactivation curves of INa were shifted slightly by 10 microM JKL1073A but more significantly by 3 microM quinidine to negative potential. Though steady state inactivation of INa was not significantly changed by 3 microM JKL1073A, the time constant of INa recovery from inactivation state was partially prolonged from 51.7 +/- 18.5 ms to 74.1 +/- 23.8 ms. Quinidine (3 microM) prolonged the time course of INa recovery from inactivation with an associated increase of slow recovery component. Inhibition of INa by JKL1073A and quinidine was increased when cells were stimulated at higher frequency. The maximal INa obtained in cells held at -140 mV was significantly decreased by 10 microM quinidine to 45.3 +/- 2.5% of control but only partially suppressed by 10 microM JKL1073A to 85.9 +/- 8.6% of control. In human atrial myocytes, JKL1073A and quinidine suppressed INa with an average IC50 of 2.4 +/- 0.6 microM and 1.4 +/- 0.3 microM, respectively. Both JKL1073A and quinidine increased the time constant of INa recovery from inactivation. In conclusion, JKL1073A at concentrations of 3 microM and 10 microM may inhibit INa mainly by binding to open and inactivated channels. Quinidine 3 microM may inhibit INa by binding to resting, open and inactivated channels. Inhibition of INa by JKL1073A may explain the inhibition of the action potential upstroke and contribute partially to its antiarrhythmic activity.
    [Abstract] [Full Text] [Related] [New Search]