Spontaneous activity of mouse detrusor smooth muscle and the effects of the urothelium

Abstract

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.

Evidence of increased centrally enhanced bladder compliance with ageing in a mouse model

“…Similar micromotional activity has been detected during human bladder filling, and is more marked in those with increased sensation [15]. Isolated bladder strips in animal models including mouse show autonomous low amplitude repetitive contractions occurring at similar low frequencies (0.02-0.03 Hz) [16,17], thus suggesting whole bladder contractile activity is intrinsic to the bladder wall. By contrast, mice and other animal cystometric models show repetitive non-voiding contractions (NVCs) of greater amplitude and frequency as the voiding threshold is approached.…”

Macroscopic electrical propagation in the guinea pig urinary bladder

“…The patches showed behavior as if there were a sudden current injection at one location and that this current then dissipated electrotonically in the surrounding area. One possibility would be a potential role for the network of vimentin-positive interstitial cells in the suburothelium region, which are connected to each other through connexin 43 as described recently (26), or from activities in the urothelium itself (38). These areas are located at the inner side of the bladder wall and away from our serosal recording electrodes, and hence we may have missed the local events that generated these current pulses.…”

“…The introduction of microelectrodes for intracellular recordings has made it possible to study in detail the electrical events in normal and diseased detrusor cells (38,46). Other technologies, such as optical mapping, have recently been introduced to study the propagation of action potentials and calcium waves in the whole bladder (30).…”

Purinergic signalling in the urinary tract in health and disease

“…Frequent ATP-mediated spontaneous depolarisations (probably sEJPs) were recorded in mouse detrusor muscle and their frequency and whole cell Ca 2+ flashes increased in the absence of the urothelium, suggesting that an inhibiting agent released from the urothelium may modulate the spontaneous activity of the bladder [485]. Spontaneous depolarisations or sEJPs were abolished by NF449, a P2X1 receptor antagonist [746].…”