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Keywords:

  • human detrusor;
  • bladder overactivity;
  • t-type Ca2+ channel;
  • l-type Ca2+ channel;
  • Ca2-activated K+-channel;
  • spontaneous activity

OBJECTIVE

To determine if bladder overactivity in humans is associated with an altered activity of Ca2+ channels in detrusor smooth muscle and the consequent activation of other ion channels.

MATERIAL AND METHODS

Samples of bladder were obtained from patients with urodynamically stable bladders, or with idiopathic detrusor overactivity. Isolated cells were patch-clamped with pipettes containing a Cs+-based filling solution to isolate inward currents, or a K+-filling solution to measure outward current. Components of inward current were separated according to their sensitivity to NiCl2 (≤100 µm) and nifedipine.

RESULTS

Ni2+-sensitive (t-type) and nifedipine-sensitive (l-type) current was recorded in all cells. The voltage- and time-dependent properties were similar in cells from both patient groups. However, the current density of the l-type current was less, and that of the t-type current was greater, in myocytes from overactive bladders. In cells from overactive bladders, the mean K+ current over the range − 80 to − 50 mV was also higher than in control cells. This current was sensitive to the large-conductance channel modulator iberiotoxin and to NiCl2 (100 µm)

CONCLUSIONS

Detrusor myocytes from overactive human bladders have a higher t-type Ca2+ current density; we propose that this increases transient outward currents, and so might contribute to higher levels of spontaneous activity.