Properties of urethral rhabdosphincter motoneurons and their regulation by noradrenaline.
The urethral rhabdosphincter (URS), commonly known as the external urethral sphincter, facilitates urinary continence by constricting the urethra. Striated muscle fibres in the urethral rhabdosphincter are innervated by Onuf's nuclei motoneurons in the spinal cord. Although noradrenaline (NA) reuptake inhibitors are shown to increase URS tone preventing urinary leakage in incontinent patients, whether or how NA affects URS motoneurons is unknown. Properties of dye-labelled URS motoneurons were investigated by whole-cell patch-clamp recordings in isolated spinal cord slices prepared from neonatal female rats. As previously shown for adult sphincter motoneurons, neonatal URS motoneurons are more depolarized and possess higher input resistance than other spinal α-motoneurons. These distinct properties make URS motoneurons more excitable than other α-motoneurons. Moreover, bath application of noradrenaline (NA) significantly depolarizes URS motoneurons and in many cases evokes action potentials. NA also significantly increases input resistance and reduces rheobase. These changes are reversed with wash, are largely blocked by the α(1)-adrenoceptor-selective antagonist prazosin, and are mimicked by the α(1)-adrenoceptor-selective agonist phenylephrine. In addition, NA significantly reduces the amplitude of the afterhyperpolarization and increases action potential frequency. Both the increase in action potential frequency and the reduction in afterhyperpolarization are occluded by apamin, a small-conductance calcium-activated potassium (SK(Ca)) channel blocker. In conclusion, NA effectively increases the excitability of URS motoneurons through multiple mechanisms. The NA-induced increase in excitability of urethral rhabdosphincter motoneurons could be a key mechanism by which NA reuptake inhibitors improve stress urinary incontinence.
Yashiro
Koji
K
Urogenix, Inc, PO Box 12035, Durham, NC 27709, USA.
Thor
Karl B
KB
Burgard
Edward C
EC
D000818:Animals; D000831:Animals, Newborn; D005260:Female; D008564:Membrane Potentials / Q000502:physiology; D009046:Motor Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D014521:Urethra / Q000502:physiology*
D024681:Potassium Channels, Calcium-Activated; D018340:Receptors, Adrenergic, alpha-1; D009638:Norepinephrine