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Decreased maternal dietary protein intake during pregnancy alters large conductance, calcium‐activated K channel (BKCa) function in fetal coronary artery smooth muscle cells
Author(s) -
Shukla Praveen,
Modgil Amit,
Sun Chengwen,
Vonnahme Kimberly,
Schauer Christopher,
Caton Joel,
Reynolds Larry,
O'Rourke Stephen
Publication year - 2011
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.25.1_supplement.1025.7
Subject(s) - iberiotoxin , fetus , medicine , endocrinology , offspring , pregnancy , calcium , chemistry , biology , genetics
We have shown that maternal nutrient restriction during pregnancy impairs an EDHF‐like pathway that is mediated via BK Ca activation in fetal coronary arteries (CA). We hypothesized that BK Ca activity is altered in CA of fetuses from malnourished ewes. Pregnant ewes were fed diets that differed only in metabolizable protein levels (control = 100% vs low protein = 80% of NRC recommendation) from day 100 – 130 of gestation. Fetal CA were then harvested and whole‐cell K currents (−70 to +50mV, 200 ms duration) were obtained in freshly isolated smooth muscle cells (n = 5–6 cells/fetus). In fetal CA smooth muscle cells from ewes fed a low protein diet, the I‐V curve was shifted to the left and peak current density was increased by 31% (low protein = 92.3 ± 7.5 vs. control = 70.5 ± 6.8 pA/pF; n=14). Iberiotoxin (100 nM) almost completely inhibited the K current in cells from the low protein group (72.3 ± 4.8% inhibition), but only partially inhibited this current in controls (31.5 ± 6.2% inhibition). Expression and localization of BK Ca α‐ and β 1 ‐subunits was similar in CA from both groups. Restricted maternal protein intake during late pregnancy enhances BK Ca activity in fetal CA, without altering BK Ca expression or localization, and may represent an adaptation to the dysfunction in the coronary arterial EDHF‐like pathway previously observed in offspring of ewes subjected to decreased nutrient intake during pregnancy (NIH R03HD061532) .