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In Vivo Pharmacological Alterations of Murine Carotid Body Responses to Hypoxia: The Role of BK Channels in Hypoxic Sensitivity
Author(s) -
Pichard Luis,
Sgambati Francis,
Kostuk Eric,
Bashai Pejmon,
Fitzgerald Robert,
Shirahata Machiko
Publication year - 2010
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.24.1_supplement.1026.21
Subject(s) - bk channel , carotid body , chemistry , in vivo , hypoxia (environmental) , anesthesia , pharmacology , electrophysiology , biophysics , endocrinology , medicine , membrane potential , biology , biochemistry , oxygen , microbiology and biotechnology , organic chemistry
Since the discovery of hypoxic inhibition of large‐conductance calcium‐activated K (BK) channels in the rat carotid body (CB), mechanisms of hypoxic sensitivity have been investigated mostly in vitro . Moreover, little is known about the role that BK channels play in the in vivo CB. The aim of this study is to explore the role that BK channels play in the hypoxic sensitivity of the in vivo murine CB. We have previously found the CB of the DBA/2J mice to have a higher expression of BK channels when compared to the A/J strain. However, BK channel opener(s) can still activate BK channels in the A/J's CB. Subsequently, hypoxia will inhibit activated BK channels, resulting in an increased neural activity. DBA/2J and A/J mice were anesthetized and artificially ventilated. Carotid sinus chemoreceptor neural activity was recorded from the central end just prior to its junction to the glossopharyngeal nerve using a glass suction pipette. Baroreceptor activity was mechanically disrupted. Following a baseline recording, the inspired gases were lowered from hyperoxia to FIO2=0.21, 0.15 and 0.10. Subsequently, we filled the space surrounding the CB with Krebs containing NS1619 to activate BK channels. After 10 minutes, the hypoxic challenge was repeated. We observed decreased baseline neural activity after application of NS1619 in both strains, suggesting opening of BK channels and hyperpolarization of cells. Also, alterations of hypoxic responses in the A/J strain became faster and more significant (although lower than DBA/2J's responses) under NS1619. Our results suggest that BK channels play a role in the hypoxic response of the murine CB in vivo . Support: F31HL096450, HL081345, AHA 09GRNT2080158, HL50712, HL61596.