Reverse mode of sodium/calcium exchanger subtype 1 contributes to detrusor overactivity in rats with partial bladder...

To investigate whether the reverse mode of sodium/calcium exchanger subtype 1 (NCX1) plays an important role in the excitability of detrusor cells in rats with partial bladder outflow obstruction (PBOO), PBOO was maintained for 6 weeks in forty female Wistar rats. Thirty of the animals exhibited non-voiding bladder contraction and comprised the DO group. An additional thirty sham-operated female Wistar rats were used as the control group. The expression levels of NCX1 were compared between the two groups by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), western blotting (WB), and double-label immunofluorescence. The contractions of detrusor strips in NCX reverse mode were measured in both groups using isometric tension. The role of NCX in the regulation of the intracellular Ca²⁺ concentration ([Ca²⁺]_i) of smooth muscle cells was observed in reverse mode using confocal microscopy, and the current was evaluated in the presence of the antagonist KB-R7943 (5 μM and 10 μM) using the whole-cell patch-clamp technique. The expression of NCX1 was significantly higher in the DO group than in the control group, as assessed by qRT-PCR, WB analysis and immunofluorescence. The volume and rate of Ca²⁺ ion flux through the NCX, as well as the NCX currents, were higher in the DO group than in the control group in both modes. Increased NCX1 levels may contribute to the establishment of DO after PBOO by elevating [Ca²⁺]_i in reverse mode under depolarization, potentially inducing cell excitability.