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Departments of 1 Urology and 2 Physiology and Biophysics, Institute for Smooth Muscle Biology, Albert Einstein College of Medicine, Bronx, New York 10461; and 3 Department of Clinical Pharmacology, Lund University Hospital, S-221 85 Lund, Sweden
Bladder overactivity associated with
outflow obstruction is a common human condition recapitulated in the
female rat by narrowing the diameter of the urethra. The goal of these
studies was to evaluate the role of intercellular communication through
connexin43 (Cx43)-derived gap junction channels to bladder overactivity
following partial urethral outflow obstruction of 3-day to 6-wk
duration. Cx43 mRNA and protein expression were barely detectable by
Northern or Western blots, respectively, in the detrusor layer of
normal bladders, but bands were found with both techniques after 6 wk of obstruction. Linear regression analysis of the RT-PCR data revealed
a statistically significant positive correlation between the duration
of obstruction (again, ranging from 3-day to 6-wk duration) and Cx43
mRNA transcript levels, such that after 6 wk of obstruction, Cx43
transcript levels were 
15-fold greater than initial control values.
When taking into account the approximately fivefold increase in bladder
weight over this same time frame, the absolute amount of Cx43 mRNA in
the bladder apparently increased by 75-fold. In that regard, as
anticipated, and consistent with previous observations, 6 wk of
obstruction was also associated with a significant increase in
spontaneous bladder contractions between micturitions. The amplitude of
these contractions was significantly reduced by heptanol given
intravesically. Furthermore, carbachol-precontracted bladder strips
from obstructed animals were more sensitive to heptanol-induced
relaxation (100 µM) than their unobstructed counterparts
(n = 6; P < 0.01). When bladder strips
were equivalently precontracted via electrical field stimulation (EFS;
20 Hz), similar heptanol-induced relaxation responses were observed.
However, the tetrodotoxin-resistant portion of the EFS-induced contraction was greater in the obstructed than in the unobstructed animals, and this portion of the contractile response was more sensitive to heptanol-induced relaxation in obstructed than
unobstructed bladders (n = 7; P < 0.01). Taken together, these observations indicate that partial outlet
obstruction produces an overactive bladder that may be more dependent
on intercellular communication through gap junctions for modulation of
contractile responses than its normal counterpart.
tissue and cellular physiology; gap junction; smooth muscle; electrical field stimulation; cystometry
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