Spontaneous purinergic neurotransmission in the mouse urinary bladder

John Young, E. Meng, T. Cunnane, K. Brain

Research output: Contribution to journalArticlepeer-review


Spontaneous purinergic neurotransmission was characterized in the mouse urinary bladder, a model for the pathological or ageing human bladder. Intracellular electrophysiological recording from smooth muscle cells of the detrusor muscle revealed spontaneous depolarizations, distinguishable from spontaneous action potentials (sAPs) by their amplitude (< 40 mV) and insensitivity to the L-type Ca2+ channel blocker nifedipine (1 μm) (100 ± 29%). Spontaneous depolarizations were abolished by the P2X1 receptor antagonist NF449 (10 μm) (frequency 8.5 ± 8.5% of controls), insensitive to the muscarinic acetylcholine receptor antagonist atropine (1 μm) (103.4 ± 3.0%), and became more frequent in latrotoxin (LTX; 1 nm) (438 ± 95%), suggesting that they are spontaneous excitatory junction potentials (sEJPs). Such sEJPs were correlated, in amplitude and timing, with focal Ca2+ transients in smooth muscle cells (measured using confocal microscopy), suggesting a common origin: ATP binding to P2X1 receptors. sAPs were abolished by NF449, insensitive to atropine (126 ± 39%) and increased in frequency by LTX (930 ± 450%) suggesting a neurogenic, purinergic origin, in common with sEJPs. By comparing the kinetics of sAPs and sEJPs, we demonstrated that sAPs occur when sufficient cation influx through P2X1 receptors triggers L-type Ca2+ channels; the first peak of the differentiated rising phase of depolarizations – attributed to the influx of cations through the P2X1 receptor – is of larger amplitude for sAPs (2248 mV s−1) than sEJPs (439 mV s−1). Surprisingly, sAPs in the mouse urinary bladder, unlike those from other species, are triggered by stochastic ATP release from parasympathetic nerve terminals rather than being myogenic.
Original languageEnglish
Pages (from-to)5743-5755
Number of pages13
JournalThe Journal of Physiology
Issue number23
Publication statusPublished - 2008


Dive into the research topics of 'Spontaneous purinergic neurotransmission in the mouse urinary bladder'. Together they form a unique fingerprint.

Cite this