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Extracellular Mg2+ blocks endothelin-1-induced contraction through the inhibition of non-selective cation channels in coronary smooth muscle

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Abstract

This study investigated the effects of changing the extracellular [Mg2+] ([Mg2+]o) on endothelin-1 (ET-1)-induced contraction of rabbit coronary artery smooth muscle and the involvement of non-selective cation (NSC) channels in this response. Increased [Mg2+]o shifted the concentration/contraction relationship curve of ET-1 to the right. In whole-cell patch clamp recordings, ET-1 (10−7 M) induced a long-lasting inwards current (94.7±7.2 pA) that was inhibited by 8 mM [Mg2+]o (45.3±4.4%) and NSC channel blockers (10−3 M streptomycin and 10−3 M La3+), but not by the voltage-dependent Ca2+ channel blocker nicardipine. The current/voltage (I/V) curve was linear. Furthermore, in pressurized arteries, the ET-1-induced contraction was also inhibited by La3+ and streptomycin, but not by nicardipine. U-73122, a selective phospholipase C (PLC) inhibitor and staurosporine and GF 109203X, which block protein kinase C (PKC), reduced ET-1-activated NSC currents by 54.2±5.1%, 60.3±5.5% and 48.5±2.9%, respectively. The inwards current was increased by 1-oleoyl-2-acetyl-sn-glycerol (OAG) and phorbol 12,13-dibutyrate (PDBu), which activate PKC selectively. Like transient receptor potential channel (TRPC3) currents, ET-1-activated NSC currents had a linear I/V relationship, were blocked by flufenamate and activated by a diacylglycerol analogue. These results suggest that [Mg2+]o blocks ET-1-induced contraction of coronary arteries by inhibiting NSC channels. Activation of PLC and PKC might be involved in activation of NSC channels.

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Acknowledgements

This work was supported by BK21 Human Life Sciences of Ministry of Education and by National Research Laboratory Grant from Ministry of Science and Technology.

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  1. Department of Physiology and National Research Laboratory for Cellular Signalling, Seoul National University College of Medicine, 28 Yonkeun-Dong, Chongno-Ku, 110-799, Seoul, Korea

    Eun A. Ko, Won Sun Park & Yung E. Earm

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Ko, E.A., Park, W.S. & Earm, Y.E. Extracellular Mg2+ blocks endothelin-1-induced contraction through the inhibition of non-selective cation channels in coronary smooth muscle. Pflugers Arch - Eur J Physiol 449, 195–204 (2004). https://doi.org/10.1007/s00424-004-1319-9

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