title: Extracellular Mg(2+) blocks endothelin-1-induced contraction through the inhibition of non-selective cation channels in coronary smooth muscle.
abstract: This study investigated the effects of changing the extracellular [Mg(2+)] ([Mg(2+)](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 [Mg(2+)](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 [Mg(2+)](o) (45.3+/-4.4%) and NSC channel blockers (10(-3) M streptomycin and 10(-3) M La(3+)), but not by the voltage-dependent Ca(2+) channel blocker nicardipine. The current/voltage (I/V) curve was linear. Furthermore, in pressurized arteries, the ET-1-induced contraction was also inhibited by La(3+) 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 [Mg(2+)](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.
authors.affiliation: 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.
authors.forename: Eun A
authors.initials: EA
authors.lastname: Ko
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Yung E
authors.initials: YE
authors.lastname: Earm
mesh_terms: D000818:Animals; D002412:Cations / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D019332:Endothelin-1 / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D002412:Cations; D019332:Endothelin-1; D007473:Ion Channels; D011493:Protein Kinase C; D010738:Type C Phospholipases; D008274:Magnesium