| Autor: |
Gagov H; Institute of Biophysics, Bulgarian Academy of Sciences, Acad. Georgi Bonchev Str., bldg. 21, 1113 Sofia, Bulgaria., Kadinov B, Hristov K, Boev K, Itzev D, Bolton T, Duridanova D |
| Jazyk: |
angličtina |
| Zdroj: |
Pflugers Archiv : European journal of physiology [Pflugers Arch] 2003 Jul; Vol. 446 (4), pp. 412-21. Date of Electronic Publication: 2003 May 22. |
| DOI: |
10.1007/s00424-002-1003-x |
| Abstrakt: |
Carbon monoxide (CO) is well known as a relaxing substance in the vasculature, where it is released during the heme oxygenase (HO) reaction. Little is known about the tissue-specific targets of CO in smooth muscles. To date the functional role of CO in the coronary artery remains unclear. The expression of HO-2, the constitutive isoform of HO, but not of HO-1 (inducible HO isoform) was demonstrated by immunohistochemical reaction. Contractile studies, performed under isometrical conditions, showed that CO, as well as hemin (given as a substrate for HO), relax de-endothelized coronary smooth muscle after the blockade of neuronal transmission. The action of hemin was antagonized by preliminary treatment of the vessel with SnPPIX--a competitive inhibitor of HO. The relaxatory effects of hemin were abolished in the presence of guanylyl-cyclase or protein kinase G antagonists. Patch-clamp studies revealed that hemin caused activation of iberiotoxin-blockable K outward current (I(K)) via guanylyl-cyclase and protein-kinase-G-dependent mechanisms. This activation coincided with hyperpolarization of the plasma membrane of single coronary smooth muscle cells by 8+/-3 mV, which was prevented by preliminary exposure of cells to 10 microM SnPPIX. The I(K)-augmenting effect of hemin was not affected by pretreatment of cells with cyclopiazonic acid and/or ryanodine, blockers of phospholipase C or heparin (applied via pipette), but was not observed when ATP was omitted from the dialyzing solution, or in the presence of Na-free, ATP-containing pipette solution. The omission of Ca(2+) from the bath or the replacement of Na with Li in both pipette and bath media also prevented the I(K)-activating effect of hemin. These results suggest that the constitutive HO-2 in coronary artery smooth muscle cells plays role in the modulation of tone. At the level of smooth muscle cells CO and its precursor hemin may cause hyperpolarization of the plasma membrane by activation of iberiotoxin-sensitive I(K) presumably via PKG-dependent activation of the Na/Ca exchanger. This activation is thought to increase the submembrane Ca(2+) concentration in the vicinity of large-conductance, Ca(2+)-sensitive K channels, thus causing voltage-dependent inhibition of Ca(2+) entry and subsequent relaxation of the vessel. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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