Inhibition of L-type Ca2+ current by ginsenoside Rd in rat ventricular myocytes

Abstract Background Ginsenoside Rd (GSRd), one of the most abundant ingredients of Panax ginseng , protects the heart via multiple mechanisms including the inhibition of Ca 2+ influx. We intended to explore the effects of GSRd on L-type Ca 2+ current ( I Ca,L ) and define the mechanism of the suppression of I Ca,L by GSRd. Methods Perforated-patch recording and whole-cell voltage clamp techniques were applied in isolated rat ventricular myocytes. Results (1) GSRd reduced I Ca,L peak amplitude in a concentration-dependent manner [half-maximal inhibitory concentration (IC 50 ) = 32.4 ± 7.1 μmol/L] and up-shifted the current–voltage ( I – V ) curve. (2) GSRd (30 μmol/L) significantly changed the steady-state activation curve of I Ca,L ( V 0.5 : −19.12 ± 0.68 vs. −16.26 ± 0.38 mV; n  = 5, p I Ca,L from inactivation [the time content (ζ) from 91 ms to 136 ms, n  = 5, p n  = 10) vs. 31.4 ± 5.2% ( n  = 5), p G i protein inhibitor ) completely abolished the I Ca,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 H -[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 I Ca,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 I Ca,L through pertussis toxin-sensitive G protein (G i ) and a nitric oxide–cyclic guanosine monophosphate-dependent mechanism.