Premium
Stimulation of M3 but not M2 muscarinic receptor type inhibits large‐conductance Ca 2+ activated K + channel in rat detrusor smooth muscle
Author(s) -
Parajuli Shankar Prasad,
Petkov Georgi V
Publication year - 2013
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.27.1_supplement.923.10
Subject(s) - bk channel , methoctramine , thapsigargin , muscarinic acetylcholine receptor , chemistry , carbachol , biophysics , ryanodine receptor , endocrinology , stimulation , receptor , medicine , patch clamp , detrusor muscle , muscarinic acetylcholine receptor m2 , membrane potential , intracellular , biology , biochemistry , smooth muscle
Large conductance Ca 2+ ‐activated K + (BK) channel is a major regulator of detrusor smooth muscle (DSM) contractility. Whether the regulation of BK channel function is mediated by muscarinic receptors (M‐Rs) remains unexplored. We studied the functional link between BK channels and M‐Rs in freshly isolated DSM cells using the perforated patch‐clamp technique. Carbachol (CCh) initially elicited large outward BK currents followed by inhibition of the amplitude and frequency of transient BK currents (TBKCs). CCh also inhibited the spontaneous transient hyperpolarizations and depolarized the cell membrane potential (MP). CCh inhibitory effects on the BK channels were suppressed by selectively blocking the M3‐Rs with 4‐DAMP, but not M2‐Rs with methoctramine. Blocking the IP 3 receptors with xestospongin C attenuated CCh‐evoked initial effects on the large outward BK currents without altering the TBKCs suggesting an involvement of Ca 2+ release from IP 3 receptors in the initiation of the large outward BK currents. In the presence of thapsigargin, ryanodine, and nifedipine – CCh did not change the steady‐state BK currents suggesting requirement of intracellular Ca 2+ in the BK channel inhibition by cholinergic pathways. In conclusion, our results revealed that stimulation of M3‐Rs, but not M2‐Rs inhibits TBKCs, depolarized MP, and promotes DSM contractions. Supported by NIH DK08424 to GVP and AUA Fellowship to SPP.