Muscarinic M2 receptors inhibit Ca2+-activated K+ channels in rat bladder smooth muscle
Takayuki Nakamura1, Junko Kimura, Osamu Yamaguchi
1Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan. takanaka@fmu.ac.jp
Purpose:
To clarify the functional relationship between M2 muscarinic receptor and Ca2+-activated K+ channel, we investigated the effect of carbachol (CCh) on the membrane current of rat bladder smooth muscle cells.
Methods:
Rat bladder single smooth muscle cells were patch clamped with whole-cell configuration.
Results:
CCh (10 micro mol/L) transiently induced an outward current in the presence of K+ in the pipette solution. A high Ca2+ concentration in the pipette solution persistently induced an outward current, which was inhibited by CCh. In the presence of M2 inhibitor, AFDX-384, CCh induced the outward current persistently, indicating that M2 was involved in the current inhibition. In pertussis toxin pretreated cells, CCh did not apparently inhibit the outward current. The CCh-induced outward current was inhibited by iberiotoxin, a selective inhibitor of large-conductance Ca2+-activated K+ channels (BKCa).
Conclusion:
CCh induces BKCa, which is inhibited by M2- and Gi-mediated signal transduction pathway. This M2-mediated pathway may enhance contraction which is initiated by M3-stimulation in rat bladder smooth muscle.
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