Muscarinic M2 receptors inhibit Ca2+-activated K+ channels in rat bladder smooth muscle.
OBJECTIVE
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).


CONCLUSIONS
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.
Nakamura
Takayuki
T
Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan. takanaka@fmu.ac.jp
Kimura
Junko
J
Yamaguchi
Osamu
O
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000502:physiology*; D014118:Toxins, Biological / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D014118:Toxins, Biological; C064719:iberiotoxin; D002217:Carbachol; D037342:Pertussis Toxin