کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4355395 1615615 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
M2 muscarinic ACh receptors sensitive BK channels mediate cholinergic inhibition of type II vestibular hair cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی سیستم های حسی
پیش نمایش صفحه اول مقاله
M2 muscarinic ACh receptors sensitive BK channels mediate cholinergic inhibition of type II vestibular hair cells
چکیده انگلیسی

There are two types of hair cells in the sensory epithelium of vestibular end organ. Type II vestibular hair cell (VHC II) is innervated by the efferent nerve endings, which employ a cholinergic inhibition mediated by SK channels through the activation of α9-containing nAChR. Our previous studies demonstrated that a BK-type cholinergic inhibition was present in guinea pig VHCs II, which may be mediated by an unknown mAChR. In this study, BK channel activities triggered by ACh were studied to determine the mAChR subtype and function. We found the BK channel was insensitive to α9-containing nAChR antagonists and m1, m3, m4 muscarinic antagonists, but potently inhibited by the m2 muscarinic antagonist. Muscarinic agonists could mimic the effect of ACh and be blocked by m2 antagonist. cAMP analog activated the BK current and adenyl cyclase (AC) inhibitor inhibited the ACh response. Inhibitor of Giα subunit failed to affect the BK current, but inhibitor of Giα and Giβγ subunits showed a potent inhibition to these currents. Our findings provide the physiological evidence that mAChRs may locate in guinea pig VHCs II, and m2 mAChRs may play a dominant role in BK-type cholinergic inhibition. The activation of m2 mAChRs may stimulate Giβγ-mediated excitation of AC/cAMP activities and lead to the phosphorylation of Ca2+ channels, resulting in the influx of Ca2+ and opening of the BK channel.


► We show that the opening of BK channel in type II vestibular hair cells is mediated by the m2 mAChR, but not α9-containing nAChR.
► The activation of m2 mAChR is coupled with the Giβγ-mediated excitation of AC/cAMP signal transduction pathway.
► m2 mAChR plays a dominant role in BK-type cholinergic inhibition in type II vestibular hair cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Hearing Research - Volume 285, Issues 1–2, March 2012, Pages 13–19
نویسندگان
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