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Chronic sustained and intermittent hypoxia reduce expression of ATP‐sensitive K+ (K‐ATP) channel subunits in the caudal NTS
Author(s) -
Carreno Flavia R.,
Zhang Weirong,
Cunningham Tom,
Mifflin Steve
Publication year - 2008
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.22.1_supplement.960.18
Subject(s) - medicine , hypoxia (environmental) , endocrinology , kir6.2 , potassium channel , chemistry , protein subunit , biology , biochemistry , organic chemistry , oxygen , gene
Tissue hypoxia induces a K‐ATP channel mediated outward current in many brainstem neurons which is considered to serve a neuroprotective function. K‐ATP channels are made up by potassium channel subunits (Kir6.1 or Kir6.2) and sulphonylurea receptor subunits. The K‐ATP channel pore is formed by Kir6 subunits. The impact of chronic exposure to either normoxia (NORM), sustained hypoxia (SH; 7 days at 10% FIO2) or intermittent hypoxia (IH; alternating 3 min periods of 21% O2 with 10% O2 for 8 hr/day, 7 days) on the expression of the K‐ATP channel subunits was examined in NTS dissected from 1mm thick sections caudal to calamus. Tissue was homogenized by sonication in modified RIPA buffer plus protease inhibitors and 5μg of the total lysate was subjected to Western Blot analysis for both Kir6.1 and Kir6.2. Densitometric analysis showed that in the caudal NTS the ratio of Kir6.1:actin was .34 ± .06 in NORM rats (n=4) and this ratio was reduced to .13 ± .01 in SH rats (n=3, p<.05) and to .08 ± .01 in IH rats (n=4, p<.01). The ratio of Kir6.2:actin was .38 ± .15 in NORM rats (n=4) and this ratio was reduced to .20 ± .01 in SH rats (n=3, p<.01) and to .13 ± .01 in IH rats (n=4, p<.001). These results suggest that the reduced K‐ATP current observed during tissue hypoxia in 2nd order chemoreceptor neurons in NTS of SH rats (Zhang & Mifflin, presented at this meeting) could be the result of a reduced expression of K‐ATP channels. Supported by HL41894 and HL62579.