Premium
Coupling of neuronal nicotinic ACh receptors to large conductance calcium‐activated K (BK) channels
Author(s) -
Otsubo Toshiki,
Fujii Koichi,
Balbir Alexander,
Okumura Mariko,
Shirahata Machiko
Publication year - 2006
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.20.4.a784-c
Subject(s) - iberiotoxin , bk channel , chemistry , nicotinic agonist , patch clamp , glomus cell , acetylcholine receptor , endocrinology , medicine , biophysics , receptor , voltage dependent calcium channel , membrane potential , microbiology and biotechnology , calcium , biology , potassium channel , biochemistry , chemoreceptor , organic chemistry
Inhibition of BK channels by hypoxia may play a role for hypoxic chemotransduction in glomus cells of the carotid body (CB). The BK channel activity is controlled by membrane potential and intracellular Ca 2+ . In general, voltage‐gated Ca 2+ channels couple to BK channel activation in neurons. We have previously shown that nicotinic ACh receptors (nAChRs) are a major Ca 2+ channels in GCs. Thus, nAChRs may functionally couple to BK channels in GCs. To test this hypothesis, we first examined the presence of nAChRs in the CB of CB57BL/6J mice. Immunohistochemistry and RT‐PCR analysis revealed that GCs express α3, α4, and β2 nAChR subunits. In the second set of experiments, patch clamp techniques were applied to measure BK channel activity in GCs of α3 and β2 nAChR KO mice. In wild type mice (+/+; CB57BL/6J), both iberiotoxin (a BK channel antagonist; Ibx) and hypoxia similarly attenuated voltage‐dependent K current. The results are similar to our previous study using DBA/2J mice. However, in β2 (−/−) mice, neither Ibx nor hypoxia inhibited K current. The effects of Ibx and hypoxia on K current in β2 (+/−) mice was intermediate between (+/+) and (−/−) mice. Similar results were observed in α3 KO mice. The data support the hypothesis and suggest that the coupling of nAChRs to BK channels may be important for hypoxic sensing of CB. Supported by AHA0255358N and HL 72293.