Inhibitory effects of retigabine, a Kv7 channel activator, on mechanosensitive primary bladder afferent activities and nociceptive behaviors in rats

Abstract

Kv7 channels are likely to be implicated in inhibition of bladder mechano- and nociceptive sensory transduction. Neurourol. Urodynam. 36:280-285, 2017. © 2015 Wiley Periodicals, Inc.

Electrophysiological properties of lumbosacral primary afferent neurons innervating urothelial and non-urothelial layers of mouse urinary bladder

“…Both urothelial and non-urothelial neurons exhibited substantial M-currents, mediated by the Kv7 family of channels encoded by KCNQ genes. Kv7 expression in primary afferents has been shown to contribute to neuronal excitability in trigeminal and DRG neurons, including those innervating the bladder [34-37]. Larger M-currents have been shown to be associated with single AP firing pattern in sensory neurons [38].…”

The KV7 channel activator retigabine suppresses mouse urinary bladder afferent nerve activity without affecting detrusor smooth muscle K+ channel currents

“…To examine other roles for K V 7 channels in the urinary bladder, we tested the effects of K V 7 modulators on urinary bladder afferent nerve activity. Retigabine has been reported to inhibit mechanosensitive primary bladder afferent nerves in the rat (Aizawa et al 2017), a possibility we sought to explore in the mouse using an ex vivo bladder preparation. We previously showed that the major part of the afferent nerve activity generated by the bladder occurs as bursts during TCs, and that these bursts could be simulated by gently compressing the bladder wall (Heppner et al 2016).…”

“…K V 7 channels have a prominent role in both the central and peripheral nervous systems, including sensory nerves that innervate the urinary bladder (Brown & Passmore, ; Aizawa et al . ). K V 7.1–7.4 transcripts have been detected in whole‐bladder extracts from guinea pig and rat, whereas primarily K V 7.2 and K V 7.3 are reported in guinea pig UBSM (Svalø et al .…”

“…These channels have been well-characterized in nerves and in the heart, where they regulate neuronal resting membrane potential and cardiac myocyte repolarization, respectively (Wulff et al 2009). K V 7 channels have a prominent role in both the central and peripheral nervous systems, including sensory nerves that innervate the urinary bladder (Brown & Passmore, 2009;Aizawa et al 2017). K V 7.1-7.4 transcripts have been detected in whole-bladder extracts from guinea Lerche et al (2000), Huang & Trussell (2011) Data are reported values in expression systems (Xenopus oocytes or CHO cells).…”

Attenuated lipopolysaccharide-induced inflammatory bladder hypersensitivity in mice deficient of transient receptor potential ankilin1

“…Each mouse was placed under a lucent plastic box and habituated to the environment for one hour. Next, bladder pain-like behavior such as licking or biting of the skin of the lower abdomen close to the bladder was monitored on a video-camera (HDR-XR500V, Sony Corporation, Tokyo, Japan) for the next 30 minutes as baseline 33 . Thereafter, the mice received intravesical LPS or saline instillation, and bladder pain-like behavior was monitored again for 30 minutes at 24, 48, and 72 hours after instillation.…”