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Hypoxic chemotransduction in two strains of mice
Author(s) -
Balbir Alexander,
Fujii Koichi,
Shirahata Machiko
Publication year - 2007
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.21.6.a925-c
Subject(s) - bk channel , chemistry , endocrinology , medicine , hypoxia (environmental) , intracellular , microbiology and biotechnology , potassium channel , biology , biochemistry , oxygen , organic chemistry
We previously reported differences in the hypoxic ventilatory, cardiovascular, and sleep‐arousal responses between two strains of mice: DBA/2J (high responder) and A/J (low responder). One paradigm of hypoxic chemotransduction in the CB revolves around the function of K + and Ca 2+ channels to increase intracellular Ca 2+ levels ([Ca]i), culminating in the release of neurotransmitters. We hypothesize that: the A/J strain has decreased expression of O 2 ‐sensitive K + channels and Ca 2+ channels, resulting an attenuated increase in [Ca]i during hypoxia; synthesis of neurotransmitters are altered in the A/J mice. CBs were harvested from 4‐week old, male mice. Our comparative microarray study showed no significant differences between the two strains in the expression of voltage‐dependent K + channels, TASK‐like K + channels, choline acetyltransferase, NO synthase 1 and tachykinin 1. However, a few ideal candidates to explain the functional differences between these two strains are revealed: BK channels, Ca 2+ channels, and tryptophan hydroxylase 1 (Tph1), an enzyme for 5‐HT synthesis. Real‐time RT‐PCR confirmed BKα, BKβ2, N‐type Ca 2+ channel α1b, Ca 2+ channel α2/δ3 and Tph1 were expressed significantly more in the DBA/2J (2.00, 8.27, 2.23, 2.53 and 6.05 fold, respectively; n= 6), while BKβ4 was less, versus the A/J. With a graded hypoxic stimulus (nadir= 53mm Hg; n =2), [Ca]i of the DBA/2J CB responded more quickly and with a larger change compared to the A/J CB. We speculate that the functional expression of BK channels, Ca 2+ channels, and 5‐HT synthesis in the DBA/2J allows for increased sensitivity to hypoxia compared to the A/J. Supported by HL72293, P30 ES 038819, AHA 0255358N, T32‐HL07534.