Calcium-dependent changes in potassium currents in guinea-pig coronary artery smooth muscle cells after acute cobalt loading in vivo.
The aim of the present study was to determine whether cobalt poisoning induces haem oxidase isoenzyme-1 (HO-1) in coronary artery smooth muscle, or accounts for any changes in coronary smooth muscle cell (SMCs) membrane ionic currents that could result from this type of heavy metal poisoning. In SMCs isolated from cobalt-treated guinea-pig coronaries, K+ channel currents (IK) were much smaller than those in cells isolated from non-treated animals. Haemin (HO substrate) increased IK concentration dependently. This effect was mimicked by 1% CO and was abolished by pretreatment of cells with a competitive HO inhibitor, by inhibitors of guanylyl cyclase, protein kinase G or phospholipase C, as well as by blocking inositol trisphosphate-dependent Ca release, or sarcoplasmic reticulum Ca-ATPase, or by bathing cells in Ca-free external solution. Expression of the Na/Ca exchanger-1 (NCX-1) protein was reduced substantially in SMCs from coronary arteries of cobalt-treated animals. No expression of HO-1 was detected. It is concluded that acute cobalt poisoning in vivo depresses Ca-sensitive K currents via CO-dependent modulation of intracellular calcium availability, most probably by suppressing the expression of NCX-1 protein.
Hristov
Kiril
K
Department of Membrane Ion Channels, Institute of Biophysics, Bulgarian Academy of Sciences, Acad. Georgi Bonchev Str., Bldg. 21, 1113 Sofia, Bulgaria.
Altankova
Iskra
I
Gagov
Hristo
H
Bolton
Thomas
T
Boev
Kiril K
KK
Duridanova
Dessislava
D
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003035:Cobalt / Q000633:toxicity*; D003331:Coronary Vessels / Q000033:anatomy & histology / Q000187:drug effects*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000378:metabolism; D006168:Guinea Pigs; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D006427:Hemin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
D015221:Potassium Channels; D019831:Sodium-Calcium Exchanger; D003035:Cobalt; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D011188:Potassium; D002118:Calcium