Cerebrosides of baifuzi, a novel potential blocker of calcium-activated chloride channels in rat pulmonary artery smooth muscle cells.
Calcium-activated chloride channels (CaCCs) are crucial regulators of vascular tone by promoting a depolarizing influence on the resting membrane potential of vascular smooth muscle cells. However, the lack of a special blocker of CaCCs has limited the investigation of its functions for long time. Here, we report that CB is a novel potential blocker of I(Cl(Ca)) in rat pulmonary artery smooth muscle cells (PASMC). Cerebrosides (CB) were isolated from Baifuzi which is dried root tuber of the herb Typhonium giganteum Engl used for treatment of stroke in traditional medicine. Using the voltage-clamp technique, sustained Ca(2+)-activated Cl(-) current (I(Cl(Ca))) was evoked by a K(+)-free pipette solution containing 500nM Ca(2+) which exhibited typical outwardly rectifying and voltage-/time-dependence characterization. Data showed that CB played a distinct inhibitory role in modulating the CaCCs. Moreover, we investigated the kinetic effect of CB on I(Cl(Ca)) and found that it could slow the activation dynamics of the outward current, accelerate the decay of the inward tail current and change the time-dependence characterization. We conclude that CB is a novel potent blocker of CaCCs. The interaction between CB and CaCCs is discussed.
Gao
Shang-Bang
SB
Institute of Biophysics and Biochemistry, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China.
Wang
Chang-Ming
CM
Chen
Xue-Song
XS
Yu
Wei-Wei
WW
Mo
Bi-Wen
BW
Li
Chen-Hong
CH
D000818:Animals; D002554:Cerebrosides / Q000494:pharmacology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology*; D051381:Rats; D013997:Time Factors
D002554:Cerebrosides; D018118:Chloride Channels; D004365:Drugs, Chinese Herbal