| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of 1 Urology and 2 Physiology and Biophysics, Institute for Smooth Muscle Biology, Albert Einstein College of Medicine, Bronx, New York 10461
The goal of these studies was to examine the potential utility of bladder instilled K+ channel gene therapy with hSlo cDNA (i.e., the maxi-K channel) to ameliorate bladder overactivity in a rat model of partial urinary outlet obstruction. Twenty-two female Sprague-Dawley rats were subjected to partial urethral (i.e., outlet) obstruction, with 17 sham-operated control rats run in parallel. After 6 wk of obstruction, suprapubic catheters were surgically placed in the dome of the bladder in all rats. Twelve obstructed rats received bladder instillation of 100 µg of hSlo/pcDNA in 1 ml PBS during catheterization, and another 10 obstructed rats received 1 ml PBS (7 rats) or 1 ml PBS containing pcDNA only (3 rats). Two days after surgery cystometry was performed on all animals to examine the characteristics of the micturition reflex in conscious and unrestrained rats. Obstruction was associated with a three- to fourfold increase in bladder weight and alterations in virtually every micturition parameter estimate. PBS-injected obstructed rats routinely displayed spontaneous bladder contractions between micturitions. In contrast, hSlo injection eliminated the obstruction-associated bladder hyperactivity, without detectably affecting any other cystometric parameter. Presumably, expression of hSlo in rat bladder functionally antagonizes the increased contractility normally observed in obstructed animals and thereby ameliorates bladder overactivity. These initial observations indicate a potential utility of gene therapy for urinary incontinence.
potassium channels; smooth muscle
This article has been cited by other articles:
|
|
 |
|
  N. D. Kanika, M. Tar, Y. Tong, D. S. R. Kuppam, A. Melman, and K. P. Davies The mechanism of opiorphin-induced experimental priapism in rats involves activation of the polyamine synthetic pathway Am J Physiol Cell Physiol, October 1, 2009; 297(4): C916 - C927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Hristov, X. Cui, S. M. Brown, L. Liu, W. F. Kellett, and G. V. Petkov Stimulation of {beta}3-adrenoceptors relaxes rat urinary bladder smooth muscle via activation of the large-conductance Ca2+-activated K+ channels Am J Physiol Cell Physiol, November 1, 2008; 295(5): C1344 - C1353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Brown, L. M. Bentcheva-Petkova, L. Liu, K. L. Hristov, M. Chen, W. F. Kellett, A. L. Meredith, R. W. Aldrich, M. T. Nelson, and G. V. Petkov {beta}-Adrenergic relaxation of mouse urinary bladder smooth muscle in the absence of large-conductance Ca2+-activated K+ channel Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1149 - F1157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Thorneloe, A. L. Meredith, A. M. Knorn, R. W. Aldrich, and M. T. Nelson Urodynamic properties and neurotransmitter dependence of urinary bladder contractility in the BK channel deletion model of overactive bladder Am J Physiol Renal Physiol, September 1, 2005; 289(3): F604 - F610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-E. Andersson and A. J. Wein Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence Pharmacol. Rev., December 1, 2004; 56(4): 581 - 631. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
