Origin of spontaneous activity in neonatal and adult rat bladders and its enhancement by stretch and muscarinic agonists

Abstract

This study examined the origin of spontaneous activity in neonatal and adult rat bladders and the effect of stretch and muscarinic agonists and antagonists on spontaneous activity. Rats were anesthetized and their bladders were excised, cannulated, and loaded with voltage- and Ca(2+)-sensitive dyes. Intracellular Ca(2+) and membrane potential transients were mapped using photodiode arrays in whole bladders, bladder sheets, or cross-section preparations at 37 degrees C. Intravesical pressure was recorded from whole bladders. In neonatal bladders and sheets, spontaneous Ca(2+) and electrical signals arose at a site near the dome and spread in a coordinated manner throughout the bladder with different dome-to-neck conduction velocities (Ca(2+): 3.7 +/- 0.4 mm/s; membrane potential: 46.2 +/- 3.1 mm/s). In whole bladders, optical signals were associated with spontaneous contractions (10-20 cmH(2)O). By contrast, in adult bladders spontaneous Ca(2+) and electrical activity was uncoordinated, originating at multiple sites and was associated with smaller (2-5 cmH(2)O) contractions. Spontaneous contractions and optical signals were insensitive to tetrodotoxin (2 muM) but were blocked by nifedipine (10 muM). Stretch or low carbachol concentrations (50 nM) applied to neonatal whole bladders enhanced the amplitude (to 20-35 cmH(2)O) of spontaneous activity, which was blocked by atropine. Bladder cross sections revealed that Ca(2+) and membrane potential transients produced by stretch or carbachol began near the urothelial-suburothelial interface and then spread to the detrusor. In conclusion, spontaneous activity in neonatal bladders, unlike activity in adult bladders, is highly organized, originating in the urothelium-suburothelium near the dome. Activity is enhanced by stretch or carbachol and this enhancement is blocked by atropine. It is hypothesized that acetylcholine is released from the urothelium during bladder filling to enhance spontaneous activity.

A morphological evaluation of botulinum neurotoxin A injections into the detrusor muscle using magnetic resonance imaging

“…Treatment of those areas with BoNT/A might be sufficient enough to reduce detrusor contractions in NDO patients, regardless of the total amount of detrusor area covered. Experimental studies in neonate and spinal cord injured rats showed that spontaneous contractile activity originated in the urothelium-suburothelium near the bladder dome [23,24]. This spontaneous activity, unlike activity in normal adult rat bladders, is highly organized, i.e.…”

“…A possible reason eventually underlying these results might be areas of detrusor tissue, which are more important for detrusor contraction and increase of local reflex activity than other areas after spinal cord injury [23]. Treatment of those areas with BoNT/A might be sufficient enough to reduce detrusor contractions in NDO patients, regardless of the total amount of detrusor area covered.…”

Mechanisms of Disease: involvement of the urothelium in bladder dysfunction

“…In addition, the close proximity of urothelial cells to myofibroblasts and bladder nerves, the sensitivity of these cells to ATP (indicated by an ATP-induced increase in intracellular Ca 2+ in afferent neurons, urothelial cells and myofibroblasts), and the evidence for cell-cell coupling mediated by gap junctions provide support for a number of physical and chemical interactions that could influence bladder function. 25,39 Activation of P2Y or P2X receptors by ATP release during bladder distension could, therefore, have a role in autocrine and paracrine signaling throughout the urothelium. This hypothesis is supported by a study published in 2005, which found that urothelial-derived ATP release in the urinary bladder purportedly acts as a trigger for exocytosis-in part via autocrine activation of urothelial purinergic (P2X and P2Y) receptors.…”

Unique properties of muscularis mucosae smooth muscle in guinea pig urinary bladder

“…The urothelium is known to release both ATP and ACh (19,41,73), and the submucosal space is richly innervated with nerve fibers that could also potentially release ATP and ACh (15,24,70). To determine whether mucosal phasic contractions were being driven by urothelial and/or neuronal release of ATP or ACh, we exposed mucosal tissue strips to atropine (20 M) to block muscarinic receptors, ␣,␤-methylene ATP (10 M) to desensitize and block P 2X purinergic receptors, or TTX (10 M) to block neuronal transmission.…”