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Overexpression of small-conductance Ca2+-activated K+ channel 2 attenuates pain-like behavior in female mice with cystitis
Guadalupe Manrique-Maldonado, Xuejiao Sun, Allison L. Marciszyn, Nicolas Montalbetti, Marcelo D. Carattino
Guadalupe Manrique-Maldonado, Xuejiao Sun, Allison L. Marciszyn, Nicolas Montalbetti, Marcelo D. Carattino
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Research Article Nephrology Neuroscience

Overexpression of small-conductance Ca2+-activated K+ channel 2 attenuates pain-like behavior in female mice with cystitis

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Abstract

Small-conductance Ca2+-activated K+ (SK) channels regulate neuronal excitability and act as a feedback mechanism to limit firing during sustained stimulation. In the present study, we demonstrated that SK2 plays an important role in the control of bladder function and visceral pain processing. SK2 channels are expressed in bladder-innervating afferent neurons, and ablation of this subunit results in elevated afferent firing rates in response to physiological levels of bladder distension, supporting a role for SK2 in modulating mechanosensory excitability. Mice overexpressing SK2 exhibit increased bladder capacity and reduced voiding frequency. Furthermore, overexpression of SK2 prevents the onset of pelvic mechanical allodynia and attenuates the exaggerated visceromotor response to bladder distension seen in wild-type mice with chemical cystitis. Thus, SK2 may be a promising target for treating overactive bladder and pain originating from the urinary bladder and other pelvic organs.

Authors

Guadalupe Manrique-Maldonado, Xuejiao Sun, Allison L. Marciszyn, Nicolas Montalbetti, Marcelo D. Carattino

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Figure 3

SK2 regulates bladder afferent firing.

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SK2 regulates bladder afferent firing.
Intravesical pressure and afferen...
Intravesical pressure and afferent discharge were recorded simultaneously during continuous filling from an ex vivo preparation. (A) Diagram of the nerve recording chamber and recording setup. (B and C) Representative recordings of intravesical pressure, raw nerve activity, and afferent discharge from a bladder of a naive control (B) and an SK2-KO mouse (C). Bladder infusion initiation is denoted by a red arrow. (D) Apparent bladder capacity in SK2-KO and WT littermate mice. Urinary bladders were infused at a rate of 15 μL/min until the intravesical pressure reached 40 cmH2O. Apparent bladder capacity represents the volume required to increase the intravesical pressure to 40 cmH2O. (E) Mean afferent nerve discharge frequency at 40 cmH2O for SK2-KO and WT littermate mice. (F) Normalized afferent discharge as a function of intravesical pressure for bladders of WT and SK2-KO mice. Data are shown as the mean ± SEM (WT, n = 6; SK2-KO, n = 7; 2-way ANOVA, *P < 0.05). (G) Bladder capacity as a function of intravesical pressure for bladders of WT and SK2-KO mice. No difference in bladder capacity versus pressure was observed between WT and SK2-KO.

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