The association between T-type Ca2+ current and outward current in isolated human detrusor cells from stable and overactive bladders.
OBJECTIVE
To determine if bladder overactivity in humans is associated with an altered activity of Ca(2+) channels in detrusor smooth muscle and the consequent activation of other ion channels.


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 NiCl(2) (< or =100 microm) 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 NiCl(2) (100 microm)


CONCLUSIONS
Detrusor myocytes from overactive human bladders have a higher T-type Ca(2+) current density; we propose that this increases transient outward currents, and so might contribute to higher levels of spontaneous activity.
Sui
Gui-Ping
GP
The Institute of Urology, University College London, UK.
Wu
Changhao
C
Severs
Nicholas
N
Newgreen
Donald
D
Fry
Christopher H
CH
D000200:Action Potentials / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D020747:Calcium Channels, T-Type / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000503:physiopathology*; D001743:Urinary Bladder / Q000503:physiopathology*; D053201:Urinary Bladder, Overactive / Q000503:physiopathology*
D020747:Calcium Channels, T-Type; D002118:Calcium