Gene responsible for the urge to urinate identified

Scientists have identified the gene that senses pressure in the bladder and plays a key part in signalling the need to urinate.

Urine is sent to the bladder by the kidneys, which extract waste and excess water from the blood. Like a balloon, the bladder expands as it fills which puts tension on the organ's muscular walls, but the cell types that detect pressure and transmit these signals to the brain remained largely unknown. Now, researchers have identified the gene PIEZO2 as critical for relaying the powerful urge to urinate, which we feel a few times a day.  

'Neurologists have always known that there's a strong link between the nervous system and bladder control, both on a conscious as well as on an automatic level,' said Dr Carsten Bönnemann, senior investigator at the National Institute for Health's (NIH) National Institute of Neurological Disorders and Stroke, and one of the authors of the research. 'Our patients together with the results in the mouse models teach us how the loss of the critical sensor PIEZO2 profoundly disrupts the wiring behind normal bladder control, ultimately reshaping the bladder itself.'

Researchers from the NIH published their results in Nature, which considered deficiencies in PIEZO2 in humans as well as different gene knockout models in mice, showing the link between reduced PIEZO2 expression and urinary problems. 

Humans lacking functional PIEZO2 reported deficient bladder-filling sensation and would only feel the urge to urinate very suddenly. This suggests PIEZO2 is vital for lower-threshold bladder stretch sensing.  

PIEZO2 contains instructions for proteins that are activated when the cell is stretched or receives pressure, forming what's known as a mechanosensitive ion channel. These channels sense tension in a cell membrane and change their shape from an open or closed state. This is vital for starting or transmitting a signal to surrounding neurons.

PIEZO2 is shown to be active in the cells lining the bladder, sensing this tension and triggering neural pathways to signal this  to the central nervous system.

'Our results show how the PIEZO2 gene tightly coordinates urination,' said Dr Alexander Chesler, senior investigator, at the NIH's National Center for Complementary and Integrative Health and a senior author of the paper. 'This is a major advance in our understanding of interoception - or the sense of what's going inside our bodies.'