The association between T-type Ca2+ current and outward current in isolated human detrusor cells from stable and overactive bladders

Abstract

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: Ni 2+-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. © 2006 The Authors.