Increased connexin43-mediated intercellular communication in a rat model of bladder overactivity in vivo

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 284; no. 5; pp. 1241 - R1248
• Main Authors: Christ, George J, Day, Nancy S, Day, Michele, Zhao, Weixin, Persson, Katarina, Pandita, Raj K, Andersson, Karl-Erik
• Format: Journal Article
• Language: English
• Published: United States 01.05.2003
• Subjects: Animals; Basic Medicine; Carbachol - pharmacology; Cell Communication; Connexin 43 - genetics; Connexin 43 - metabolism; Disease Models, Animal; Farmakologi och toxikologi; Female; Gap Junctions - physiology; Gene Expression; Heptanol - pharmacology; Läkemedelskemi; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinal Chemistry; Medicinska och farmaceutiska grundvetenskaper; Muscle Contraction - drug effects; Muscle Relaxation - drug effects; Organ Size; Pharmacology and Toxicology; Rats; Rats, Sprague-Dawley; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tetrodotoxin - pharmacology; Time Factors; Urinary Bladder - drug effects; Urinary Bladder - metabolism; Urinary Bladder - physiopathology; Urinary Incontinence - metabolism; Urinary Incontinence - physiopathology
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00030.2002

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