Modulation of bladder myofibroblast activity: implications for bladder function

Abstract

Bladder suburothelial myofibroblasts may modulate both sensory responses from the bladder wall and spontaneous activity. This study aimed to characterize further these cells in their response to exogenous agents implicated in mediating the above activity. Detrusor strips, with or without mucosa, and isolated suburothelial myofibroblasts were prepared from guinea pig bladders. Isometric tension, intracellular Ca(2+), and membrane current were recorded. Cell pairs were formed by pushing two cells together. Tension, intracellular Ca(2+), and membrane potential were also recorded from bladder sheets using normal or spinal cord-transected (SCT) rats. Spontaneous contractions were greater in detrusor strips with an intact mucosa and were augmented by 10 muM UTP. ATP, UTP, or reduced extracellular pH elicited Ca(2+) transients and inward currents (E(rev) -30 mV) in isolated cells. Capsaicin (5-30 muM) reduced membrane current (37 +/- 12% of control) with minor effects on Ca(2+) transients: sodium nitroprusside reduced membrane currents (40 +/- 21% of control). Cell pair formation, without an increase in cell capacitance, augmented ATP and pH responses (180 +/- 58% of control) and reduced the threshold to ATP and acidosis. Glivec (20-50 muM) reversibly blocked the augmentation and also reduced spontaneous activity in bladder sheets from SCT, but not normal, rats. Glivec also disrupted the spread of Ca(2+) waves in SCT sheets, generating patterns similar to normal bladders. Suburothelial myofibroblasts respond to exogenous agents implicated in modulating bladder sensory responses; responses augmented by physical intercellular contact. The action of glivec and its selective suppression of spontaneous activity in SCT rats identifies a possible pathway to attenuate bladder overactivity.