Aim: 

Bladder suburothelial interstitial cells generate Ca²⁺ transients and Cl^- currents on exposure to exogenous agonists. It is hypothesised these cells modulate sensations arising from bladder filling. Because of their structural network characteristics we examined if cell-pair formation modulates their responses.

Methods: 

Guinea-pigs (300-500g) were killed by cervical dislocation according to UK Home Office guidelines and the bladder removed. Mucosa was separated from detrusor and digested in a collagenase-containing solution to generate isolated interstitial cells. Cells were loaded with Fura2, superfused with a CO₂/HCO^3- or HEPES-buffered solution and voltage-clamped (Cs-filling solution). Data are mean ± sd; differences were examined with Student's t-tests (p < 0.05).

Results: 

ATP elicited intracellular Ca²⁺ transients and inward currents at -60mV (25.8 ± 18.7pA.pF^-1, n = 29). When a cell touched firmly against a second, the response was significantly augmented by 180 ± 58% (paired t-test). However, cell capacitance was unaffected (13.6 ± 6.8 vs. 12.9 ± 6.9pF). Similar responses were observed on exposure to low pH solutions. Augmentation was absent when interstitial cells touched a detrusor myocyte. Cell pair formation also lowered the threshold response to ATP about ten-fold. With glivec (30mM) the response was not augmented by cell-pair formation (94 ± 50% of control, n = 24).

Conclusion: 

Responses of suburothelial interstitial cells to exogenous agonists are augmented by touching another cell and formation of cells into a tight network increases their functionality. Glivec deregulates tyrosine-receptor kinase activity that in turn modulates pathways also modified by adherens junction formation. Identification of such pathways will help to understand this augmentation. We thank the Wellcome Trust for support.