Aims: To characterize the detrusor muscle of the mouse urinary bladder in order to understand more precisely spontaneous contractile behavior of this organ. This study examined the spontaneous electrical activity and Ca 2þ dynamics of the detrusor smooth muscle and investigated the role of the urothelium. Materials and Methods: Detrusor smooth muscle strips were isolated from mouse bladders. The urothelium was either kept intact or removed. Changes in membrane potential were recorded using sharp electrode intracellular recording. To image Ca 2þ dynamics, tissue strips were exposed to 10 mM Oregon Green 488 BAPTA-1 AM for 70 min, and then image series were acquired with a laser-scanning confocal microscope. Results: (1) Mouse detrusor smooth muscle cells (SMCs) generate nifedipine-sensitive spontaneous action potentials (sAPs) at a low frequency (1.3 AE 0.9 min À1 , n ¼ 11) in preparations with intact urothelium. This frequency increased when the urothelium was removed (7 AE 8.3 min À1 , n ¼ 17) (P < 0.05, Student's t test). (2) Frequent ATP-mediated spontaneous depolarizations were recorded in all cells. (3) The frequency of whole cell Ca 2þ flashes of detrusor smooth muscle cells was higher in preparations with the urothelium removed (median 1.2 min À1 , n ¼ 7) than in urothelium denuded preparations (median 0.6 min À1 , n ¼ 7) (P < 0.01, Mann-Whitney U-test). Conclusions: Spontaneous activity of the mouse detrusor smooth muscles was characterized enabling future comparative work on gene knock-out strains. Evidence suggesting release of an inhibitory factor by the urothelium was apparent.
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 Ca 2+ channel blocker nifedipine (1 μm) (100 ± 29%). Spontaneous depolarizations were abolished by the P2X 1 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 Ca 2+ transients in smooth muscle cells (measured using confocal microscopy), suggesting a common origin: ATP binding to P2X 1 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 P2X 1 receptors triggers L-type Ca 2+ channels; the first peak of the differentiated rising phase of depolarizations -attributed to the influx of cations through the P2X 1 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.
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