Role of connexin 43 in the maintenance of spontaneous activity in the guinea pig prostate gland

• Published in: British journal of pharmacology 2010-12, Vol.161 (8), p.1692-1707
• Main Authors: Dey, Anupa, Kusljic, Snezana, Lang, Richard J, Exintaris, Betty
• Format: Article
• Language: English
• Subjects: age; Age Factors; Animals; Biological and medical sciences; BPH; Carbenoxolone - pharmacology; Connexin 43 - metabolism; Connexin 43 - physiology; gap junctions; Gap Junctions - drug effects; Glycyrrhetinic Acid - analogs & derivatives; Glycyrrhetinic Acid - pharmacology; Guinea Pigs; ICC; In Vitro Techniques; Male; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; Miscellaneous; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; Octanols - pharmacology; Pharmacology. Drug treatments; prostate; Prostate - drug effects; Prostate - physiology; Research Papers; slow waves; smooth muscle
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.2010.01001.x

BACKGROUND AND PURPOSE To investigate the role of connexin 43 in the maintenance of spontaneous activity in prostate tissue from young and old guinea pigs. EXPERIMENTAL APPROACH Conventional intracellular microelectrode and tension recording techniques, coupled with Western blot analysis and immunohistochemistry for connexin 43 (CX43) were used. The effects of three gap junction uncouplers, 18β glycyrrhetinic acid (10 µM, 40 µM), carbenoxolone (10 µM, 50 µM) and octanol (0.5 mM, 1 mM), were studied in cells displaying slow wave activity and on spontaneously contracting tissue from prostate glands of young (2–5 months) and old (9–16 months) guinea pigs. KEY RESULTS 18β Glycyrrhetinic acid (40 µM), carbenoxolone (50 µM) or octanol (0.5 mM) abolished slow wave activity in prostate tissue from young and old guinea pigs and depolarized membrane potential by approximately 5 mV. These treatments also abolished all contractions in both sets of prostate tissue. These effects were reversed upon washout. Western blot analysis and CX43 immunohistochemistry showed that there was no age‐related difference in the expression and distribution of CX43 in prostate tissues. CONCLUSION AND IMPLICATIONS When gap junctional communication via CX43 was disrupted, spontaneous activity was abolished at a cellular and whole tissue level; CX43 is therefore essential for the maintenance of spontaneous slow wave activity and subsequent contractile activity in the guinea pig prostate gland.