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Modulation of the vascular KATP channel by the reactive carbonyl methylglyoxal (MGO)
Author(s) -
Yang Yang,
Cui Ningren,
Jiang Chun
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1018.15
Subject(s) - methylglyoxal , chemistry , reactive oxygen species , biophysics , medicine , biochemistry , biology , enzyme
The vascular K ATP channel made of Kir6.1 and SUR2B plays an important role in systemic response and susceptibility to diabetes and sepsis in which the channel may be modulated by reactive oxygen and carbonyl species. MGO is a carbonyl glycolytic intermediate that is highly reactive. Here we show evidence for the channel modulation by MGO. Acute exposure to MGO activated the Kir6.1/SUR2B channel expressed in HEK293 cells with EC 50 ~1.5 mM. A pretreatment with a K ATP channel inhibitor completely blocked the MGO effect. In excised patches, MGO augmented P open without changing single‐channel conductance. In contrast, a prolonged treatment with MGO produced marked suppression of the K ATP currents with the time constant 3 hrs. This inhibition was associated with a reduction in Kir6.1/SUR2B mRNAs revealed by RT‐PCR and qPCR in isolated aortic rings and cultured A10 aortic smooth muscle cells. The effect of MGO did not seem to result from an inhibition of Kir6.1 mRNA synthesis, as the MGO effect remained after transcriptional inhibition with actinomycin‐D. MGO did not affect the mRNA level in cell‐free condition. In conclusion, our results suggest that MGO is a strong K ATP channel regulator, activating the channel with acute exposure and inhibiting the channel with a prolonged treatment (supported by NIH‐HL067890).