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Nerve-evoked purinergic signaling suppresses action potentials, Ca2+ flashes and contractility evoked by muscarinic receptor activation in mouse urinary bladder smooth muscle

Heppner TJ, Werner ME, Nausch B, Vial C, Evans RJ, Nelson MT

JPhysiology. 2009;.

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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.

Bibliographic metadata

Type of resource:
Content type:
Publication status:
Accepted
Publication type:
Publication form:
Published date:
Journal title:
Digital Object Identifier:
10.1113/jphysiol.2009.178806
Attached files embargo period:
Immediate release
Attached files release date:
30th September, 2014
Access state:
Active

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Record metadata

Manchester eScholar ID:
uk-ac-man-scw:53769
Created by:
Nelson, Mark
Created:
13th October, 2009, 15:13:27
Last modified by:
Nelson, Mark
Last modified:
30th September, 2014, 14:02:50

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