Daurisoline suppressed early afterdepolarizations and inhibited L-type calcium current.
Our previous studies have shown that daurisoline (DS) exerted antiarrhythmic effects on various experimental arrhythmias. In this study, the effects of DS on early afterdepolarizations (EADs) and its possible mechanisms have been investigated. Cardiac hypertrophy was induced in rabbits by coarctating the abdominal aorta. The effects of DS on action potential duration (APD) and the incidences of EADs were studied in hypertrophied papillary muscles of rabbits in the conditions of low external K(+) concentration ([K(+)]o) and dofetilide (dof) by using standard microelectrode technique. The whole-cell patch clamp was used to record the L-type calcium current (I(Ca-L)) in isolated left ventricular cells of rabbits. The results showed that in hypertrophied papillary muscles of rabbits with low [K(+)]o ([K(+)]o = 2.7 mM), 1 microM dof prolonged APD(50) and APD(90) markedly and the incidence of EADs was 66.7% (4/6, p < 0.01); when 15 microM DS was applied, the incidence of EADs was 0% (0/4, p < 0.01) and the prolonged APD was shortened (p < 0.01). In a single myocyte, DS could also inhibit EADs induced by dof, low [K(+)]o and low external Mg(2+) concentration ([Mg(2+)]o) ([Mg(2+)](o) = 0.5 mM). DS could decrease the triangulation. In a single myocyte, DS could make the I-V curve upward, shift the steady-state activation curves to the right and the steady-state inactivation curves to the left and prolong the tau value of recovery curve obviously. These results suggested that DS could inhibit EADs which may be associated with its blockade effects on I(Ca-L).
Liu
Qiang-Ni
QN
Department of Pharmacology, Huazhong University of Science and Technology, Wuhan, China.
Zhang
Li
L
Gong
Pei-Li
PL
Yang
Xiao-Yan
XY
Zeng
Fan-Dian
FD
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D044182:Benzylisoquinolines / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D020013:Calcium Signaling / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D031603:Menispermum / Q000737:chemistry*; D032342:Muscle Cells / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010627:Phenethylamines; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D027343:Rhizome; D013449:Sulfonamides; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D044182:Benzylisoquinolines; D020746:Calcium Channels, L-Type; D010627:Phenethylamines; D010936:Plant Extracts; D013449:Sulfonamides; C023968:daurisoline; C063533:dofetilide; D011188:Potassium