Pflügers Archiv

, Volume 449, Issue 2, pp 195–204

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

Smooth Muscle

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.

Keywords

Coronary artery Coronary arterial smooth muscle cell Endothelin-1 Magnesium Non-selective cation channels Protein kinase C 

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Copyright information

© Springer-Verlag  2004

Authors and Affiliations

  1. 1.Department of Physiology and National Research Laboratory for Cellular SignallingSeoul National University College of MedicineSeoulKorea

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