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KMID : 0352720150390020169
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Journal of Ginseng Research
2015 Volume.39 No. 2 p.169 ~ p.177
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Inhibition of L-type Ca2+ current by ginsenoside Rd in rat ventricular myocytes
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Lu Cheng
Sun Zhijun
Wang Line
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Abstract
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Background: Ginsenoside Rd (GSRd), one of the most abundant ingredients of Panax ginseng, protects the heart via multiple mechanisms including the inhibition of Ca2+ influx.We intended to explore the effects of GSRd on L-type Ca2+ current (ICa,L) and define the mechanism of the suppression of ICa,L by GSRd. Methods: Perforated-patch recording and whole-cell voltage clamp techniques were applied in isolated rat ventricular myocytes. Results: (1) GSRd reduced ICa,L peak amplitude in a concentration-dependent manner [half-maximal inhibitory concentration (IC50)=32.4±7.1μmol/L] and up-shifted the current-voltage (I-V) curve. (2) GSRd (30μmol/L) significantly changed the steady-state activation curve of ICa,L (V0.5:-19.12±0.68 vs. -6.26±0.38mV; n = 5, p < 0.05) and slowed down the recovery of ICa,L from inactivation [the time content (ζ) from 91 ms to 136 ms, n = 5, p < 0.01]. (3) A more significant inhibitive effect of GSRd (100μmol/L) was identified in perforated-patch recording when compared with whole-cell recording [65.7±3.2% (n = 10) vs. 31.4±5.2% (n = 5), p < 0.01]. (4) Pertussis toxin (Gi protein inhibitor) completely abolished the ICa,L inhibition induced by GSRd. There was a significant difference in inhibition potency between the two cyclic adenosine monophosphate elevating agents (isoprenaline and forskolin) prestimulation [55±7.8% (n = 5) vs. 17.2±3.5% (n = 5), p < 0.01]. (5) 1H-[1,2,4]Oxadiazolo[4,3-a]-quinoxalin-1-one (a guanylate cyclase inhibitor) and N-acetyl-L-cysteine (a nitric oxide scavenger) partly recovered the ICa,L inhibition induced by GSRd. (6) Phorbol-12-myristate-13-acetate (a protein kinase C activator) and GF109203X (a protein kinase C inhibitor) did not contribute to the inhibition of GSRd. Conclusion: These findings suggest that GSRd could inhibit ICa,L through pertussis toxin-sensitive G protein (Gi) and a nitric oxide-cyclic guanosine monophosphate-dependent mechanism.
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KEYWORD
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ginsenoside Rd, L-type calcium channels, Panax ginseng, patch-clamp techniques
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