title: Nerve-evoked purinergic signalling suppresses action potentials, Ca2+ flashes and contractility evoked by muscarinic receptor activation in mouse urinary bladder smooth muscle.
abstract: Contraction of urinary bladder smooth muscle (UBSM) is caused by the release of ATP and ACh from parasympathetic nerves. Although both purinergic and muscarinic pathways are important to contraction, their relative contributions and signalling mechanisms are not well understood. Here, the contributions of each pathway to urinary bladder contraction and the underlying electrical and Ca(2+) signalling events were examined in UBSM strips from wild type mice and mice deficient in P2X1 receptors (P2X1(-/-)) before and after pharmacological inhibition of purinergic and muscarinic receptors. Electrical field stimulation was used to excite parasympathetic nerves to increase action potentials, Ca(2+) flash frequency, and force. Loss of P2X1 function not only eliminated action potentials and Ca(2+) flashes during stimulation, but it also led to a significant increase in Ca(2+) flashes following stimulation and a corresponding increase in the force transient. Block of muscarinic receptors did not affect action potentials or Ca(2+) flashes during stimulation, but prevented them following stimulation. These findings indicate that nerve excitation leads to rapid engagement of smooth muscle P2X1 receptors to increase action potentials (Ca(2+) flashes) during stimulation, and a delayed increase in excitability in response to muscarinic receptor activation. Together, purinergic and muscarinic stimulation shape the time course of force transients. Furthermore, this study reveals a novel inhibitory effect of P2X1 receptor activation on subsequent increases in muscarinic-driven excitability and force generation.
authors.affiliation: Department of Pharmacology, Given Bldg, Room C315, 89 Beaumont Avenue, University of Vermont, Burlington, VT 05405-0068, USA. thomas.heppner@uvm.edu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Heppner
authors.forename: Matthias E
authors.initials: ME
authors.lastname: Werner
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nausch
authors.forename: Catherine
authors.initials: C
authors.lastname: Vial
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Evans
authors.forename: Mark T
authors.initials: MT
authors.lastname: Nelson
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000294:innervation* / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058469:Receptors, Purinergic P2X; D001743:Urinary Bladder / Q000294:innervation* / Q000502:physiology*
chemical_list: D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X