Electrophysiological mechanisms of sophocarpine as a potential antiarrhythmic agent.
OBJECTIVE
To examine the electrophysiological effects of sophocarpine on action potentials (AP) and ionic currents of cardiac myocytes and to compare some of these effects with those of amiodarone.


METHODS
Langendorff perfusion set-up was used in isolated guinea pig heart, and responses to sophocarpine were monitored using electrocardiograph. Conventional microelectrode, voltage clamp technique and perforated patch were employed to record fast response AP (fAP), slow response AP (sAP) and ionic currents in guinea pig papillary muscle or rabbit sinus node cells.


RESULTS
Tachyarrhythmia produced by isoprenaline (15 μmol/L) could be reversed by sophocarpine (300 μmol/L). Sophocarpine (10 μmol/L) decreased the amplitude by 4.0%, maximal depolarization velocity (V(max)) of the fAP by 24.4%, and Na(+) current (I(Na)) by 18.0%, while it prolonged the effective refractory period (ERP) by 21.1%. The same concentration of sophocarpine could also decrease the amplitude and V(max) of the sAP, by 26.8% and 25.7%, respectively, and attenuated the Ca(2+) current (I(CaL)) and the K(+) tail current substantially. Comparison of sophocarpine with amiodarone demonstrated that both prolonged the duration and the ERP of fAP and sAP, both decreased the amplitude and V(max) of the fAP and sAP, and both slowed the automatic heart rate.


CONCLUSIONS
Sophocarpine could reverse isoprenaline-induced arrhythmia and inhibit I(Na), I(CaL), and I(Kr) currents. The electrophysiological effects of sophocarpine are similar to those of amiodarone, which might be regarded as a prospective antiarrhythmic agent.
Department of Physiology, Shanghai Jiaotong University School of Medicine, China.
Zhi-fang
ZF
Yang
Ci-zhen
CZ
Li
Wei
W
Wang
Ying-min
YM
Chen
Ying
Y
Zhang
Yuan-mou
YM
Liu
Hong-wei
HW
Wang
D000200:Action Potentials / Q000187:drug effects; D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000638:Amiodarone / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D055724:Electrophysiological Phenomena; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D013610:Tachycardia / Q000188:drug therapy* / Q000503:physiopathology; D000093842:Matrines
D000470:Alkaloids; D000638:Amiodarone; D000889:Anti-Arrhythmia Agents; D012964:Sodium; C035933:sophocarpine; D000093842:Matrines
J Cardiovasc Pharmacol. 1990 Mar;15(3):398-407
1691363
Circ Res. 1987 Sep;61(3):429-35
3621502
Am J Cardiol. 1999 Nov 4;84(9A):20R-28R
10568656
Am Heart J. 1990 Oct;120(4):819-30
2171311
Biol Pharm Bull. 2009 Sep;32(9):1521-6
19721226
Yao Xue Xue Bao. 2008 Jan;43(1):44-9
18357730
Curr Cardiol Rep. 2006 Sep;8(5):349-55
16956450
J Cardiovasc Electrophysiol. 1995 Oct;6(10 Pt 2):880-6
8548109
J Cardiovasc Electrophysiol. 2009 Jul;20(7):803-10
19298559
Zhonghua Xin Xue Guan Bing Za Zhi. 2009 Jun;37(6):528-31
19927635
Circulation. 2005 Dec 13;112(24):3777-85
16344406
Br J Pharmacol. 2002 Sep;137(2):253-62
12208783
J Cardiovasc Pharmacol. 1988 Dec;12(6):621-8
2467078
Acta Pharmacol Sin. 2009 Aug;30(8):1115-22
19617895
Acta Pharmacol Sin. 2008 Apr;29(4):421-9
18358087
Expert Rev Cardiovasc Ther. 2007 Jan;5(1):9-19
17187453
Am J Physiol. 1986 Jun;250(6 Pt 2):H982-91
3717369
Cardiovasc Res. 1988 Nov;22(11):818-25
3256423
J Cardiovasc Pharmacol. 1998 Nov;32(5):783-90
9821853
J Cardiovasc Pharmacol. 1991 Jun;17(6):894-902
1714012
J Cardiovasc Electrophysiol. 1995 Oct;6(10 Pt 2):887-900
8548110
Zhongguo Yao Li Xue Bao. 1990 May;11(3):253-7
2088002
Circ Res. 2008 Jun 6;102(11):1389-97
18467626
JAMA. 2007 Sep 19;298(11):1312-22
17878423
Biophys J. 1992 Sep;63(3):654-62
1330034