Suppression of pacemaker activity by Ginkgo biloba extract and its main constituent, bilobalide in rat sino-atrial nodal cells.
Effects of Ginkgo biloba extract (GBE) and bilobalide (a main constituent) on the pacemaker activity and the underlying ionic currents in rat sino-atrial (SA) nodal cells were investigated using patch-clamp techniques. Both GBE and bilobalide depressed the pacemaker activity in a concentration-dependent manner. At both 0.03 mg/ml GBE and 0.3 microM bilobalide, a negative chronotropic effect was produced. Dysrhythmias often occurred. The L-type Ca(2+) current (I(Ca)) and the hyperpolarization-activated inward current (I(f)) decreased by 69.7+/-3.2% (n=6, P<0.001) and by 12.6+/-2.1% (n=7, P<0.05) at 0.03 mg/ml GBE, and by 51.2+/-3.3% (n=6, P<0.01) and by 19.8+/-2.2 % (n=6, P<0.05) at 0.3 microM bilobalide, respectively. The delayed rectifier K(+) current (I(K)) also decreased. The inhibition was 12.3+/-2.0% (n=6, P<0.05) at 0.03 mg/ml GBE, and was 28.0+/-2.9% (n=6, P<0.05) at 0.3 microM bilobalide. These results indicate that cardiac ionic channels contributing to the pacemaking are highly sensitive to GBE and bilobalide, which can sufficiently modify the spontaneous activity in rat SA nodal cells.
Satoh
Hiroyasu
H
Department of Pharmacology, Division of Molecular and Cellular Biology, Nara Medical University, School of Medicine, Kashihara, Nara 634-8521, Japan. hysat@naramed-u.ac.jp
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D001683:Biological Clocks / Q000187:drug effects*; D002121:Calcium Channel Blockers; D003517:Cyclopentanes / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology*; D005663:Furans / Q000494:pharmacology*; D020441:Ginkgo biloba; D046934:Ginkgolides; D007473:Ion Channels / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012849:Sinoatrial Node / Q000187:drug effects*
D002121:Calcium Channel Blockers; D003517:Cyclopentanes; D004224:Diterpenes; D005663:Furans; D046934:Ginkgolides; D007473:Ion Channels; D010936:Plant Extracts; C073710:bilobalide