Faculty of Health Sciences & Medicine

Future Research Projects

SPONTANEOUS CONTRACTILE ACTIVITY OF THE BLADDER UROTHELIUM AND ITS ROLE IN BLADDER OVERACTIVITY

Supervisor

Professor Russ Chess-Williams
Professor of Human Physiology

BACKGROUND

Bladder overactivity is a condition where the bladder spontaneously contracts during filling and this can result in intense feelings of urgency and a high frequency of micturition (bladder emptying) and in some patients even urinary incontinence.  The causes of overactive bladder are unknown, yet this condition affects more than 16% of the population over the age of 40.

Previous research in the area of bladder function and drug development has centred on the factors affecting nerve induced contraction of the bladder smooth muscle.  However recently we have discovered that the epithelial lining (urothelium) of the bladder generates a spontaneous contractile activity which probably involves ‘myofibroblast’ cells within its layers.  These cells resemble the Interstitial Cells of Cajal (ICC) of the intestine, where they act as pacemakers and are involved in regulating gastrointestinal motility.  Such a role in the bladder would implicate them in human bladder overactivity.  Little in known about this ‘epithelial contractile activity’ and what factors influence its appearance and whether this activity is involved in disease is unknown.

AIMS OF THE PROJECT

  1. Characterise the spontaneous contractile activity of the urothelium (eg. determine frequency, amplitude, effect of stretch)
  2. Identify the factors regulating urothelial spontaneous contractions (eg. Ach, noradrenaline, ATP, nitric oxide, NKA, etc)
  3. Investigate whether this activity can be demonstrated for the human urothelium.

METHODS

  • In vitro isolated tissue bath experiments to investigate contractile activity
  • Immunohistochemistry to identify the cell populations within the urothelium
  • Radioligand binding experiments to identify the receptors present in the urothelium