Activation of the iberiotoxin-sensitive BKCa channels by salvianolic acid B of the porcine coronary artery smooth muscle cells

In this study, we examined the effects of Salvia miltiorrhiza (Danshen) crude extract, some of its lipid-soluble components (tanshinone I, tanshinone II_A, cryptotanshinone, dihydroisotanshinone I) and the water-soluble compounds (danshensu and salvianolic acid B) on the K⁺ channels such as the iberiotoxin-sensitive Ca²⁺-activated K⁺ (BK_Ca) channels and the glibenclamide-sensitive ATP-dependent K⁺ (IK_ATP) channels of the porcine left anterior descending coronary artery smooth muscle cells. Cumulative application of salvianolic acid B (30-300 μM) caused a l-NNA (100 μM)-insensitive, potentiation of the outward BK_Ca current amplitude with no apparent effect on the IK_ATP channels opening. Salvianolic acid B (300 μM) caused an ODQ (10 μM, a guanylate cyclase inhibitor)-sensitive enhancement of the outward BK_Ca current amplitude. In contrast, none of the other isolated chemical constituents of S. miltiorrhiza modified the openings of the two types of K⁺ channels studied. In conclusion, our results suggest that salvianolic acid B, a major hydrophilic constituent found in Radix S. miltiorrhiza, activated the opening of the BK_Ca channels of the porcine coronary artery smooth muscle cells through the activation of guanylate cyclase without the involvement of the nitric oxide synthase activation.