The phrase “to go against the tide” means to oppose or resist what others are doing or saying. For the urethra this phrase perfectly describes its function – to provide resistance against the urinary bladder.
The urethra provides a resistance that stops any unwanted leakage of urine from the bladder: the contracted urethra is much like the valve in a tap. When the bladder needs to empty, the urethra relaxes, “opens the tap” and acts as a pipe to carry urine from the bladder. The mechanism of urethral resistance is not yet known but understanding it would have a huge impact in medicine for treating diseases such as Urinary Incontinence.
Urinary incontinence is any unintentional loss of urine. Most people associate it with a dysfunctional bladder, which squeezes out urine, but urinary incontinence can also mean a poorly functioning urethra. For example, when the urethra doesn’t contract enough to form a tightly sealed tap then an unwanted leakage of urine occurs. This type of incontinence is Stress Urinary Incontinence and can happen when you laugh hard or cough.
Stress urinary incontinence predominately affects women, especially those who have had children. To date there are no drugs available to treat it. Therefore patients are required to 1) manage the condition with absorbent pads 2) try pelvic floor strengthening exercises or 3) undergo surgery as a last resort. This is not a good enough solution for sufferers who have a poor quality of life and for society as a whole. Thus, we need to improve our knowledge of how the urethra works.
Finding out how this system works through experimental research has been the focus of my studies. From the outside the urethra appears to lie almost idle. However, if we delve deeper into the walls of the urethra, there is a whole range of cellular activity that makes this tissue all the more interesting.
One of the layers in the wall – the smooth muscle layer – holds the answer to the cellular origins of the urethral resistance. Within this layer, lie two different groups of cells: smooth muscle cells and Interstitial cells of Cajal. Researchers speculate that Interstitial cells of Cajal relay messages from nerves to smooth muscle cells causing them to contract, thereby generating urethral resistance.
We are able to record electrical activity from each of
these cells. We measured the current and voltage of the cells, similar to measuring the electric flow passing through a wire except on a much smaller scale. When we recorded electrical activity we found that smooth muscle cells are electrically quiet while Interstitial cells are electrically active. When we explored Interstitial cells further we found that the origin of this electrical activity comes from an ion channel.
Ion channels are the doormen of cells – they decide what enters and what leaves the cell. Just as a doorman checks for the correct footwear so do ion channels recognise specific characteristics and decide who’s in and who’s out. The ion channels responsible for generating electrical activity can be activated by calcium ions inside the cell and in turn let chloride ions flow out of the cell. This flow ultimately generates urethral resistance.
Identifying the origin of urethral resistance has given us the big picture, however much work remains to fill in the details. Once we understand the details the race is on to find a drug capable of activating these ion channels. These drugs could be used to treat urinary incontinence, improve patients’ quality of life and keep everyone’s urethra “going against the tide”.
About the Author
Stephen Fedigan is a third year Ph.D student at Dundalk Institute of Technology within the School of Health and Science as part of the Smooth Muscle Research Centre. His current research involves understanding the mechanism responsible for the generation of tone in urethral smooth muscle. Other interests include ion channel physiology and scientific outreach. He has presented findings at various scientific gatherings both nationally and internationally and has published a paper titled “Pharmacological characterization of TMEM16A currents” in the journal Channels.