Muscarinic M2 receptors inhibit Ca²⁺‐activated K⁺ channels in rat bladder smooth muscle

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.