K+ channel modulation of slow wave activity in the guinea‐pig prostate

• Published in: British journal of pharmacology 2007-07, Vol.151 (6), p.828-836
• Main Authors: Nguyen, D‐T T, Lang, R J, Exintaris, B
• Format: Article
• Language: English
• Subjects: 4-Aminopyridine - pharmacology; Animals; Apamin - administration & dosage; Apamin - pharmacology; Benzopyrans - pharmacology; Biological and medical sciences; Calcitonin Gene-Related Peptide - pharmacology; Cromakalim - pharmacology; Cyclopentanes - pharmacology; Dose-Response Relationship, Drug; Electrophysiology; Glyburide - pharmacology; Guinea Pigs; In Vitro Techniques; Isoproterenol - pharmacology; K+ channel blockers; Male; Medical sciences; Membrane Potentials; Nitroprusside - pharmacology; Peptides - pharmacology; Pharmacology. Drug treatments; Potassium Channel Blockers - pharmacology; Potassium Channels - agonists; Potassium Channels - physiology; prostate; Prostate - metabolism; Prostate - physiology; Research Papers; slow waves; smooth muscle; Stromal Cells - drug effects; Stromal Cells - metabolism; Tetraethylammonium - administration & dosage; Tetraethylammonium - pharmacology
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0707283

Background and purpose: The aim of this study was to investigate the role of different K+ channel populations and the inhibitory effect of various exogenously applied K+ channel openers in the regulation of slow wave activity in the guinea‐pig prostate. Experimental approach: Recordings of membrane potential were made using intracellular microelectrodes. Key results: Tetraethylammonium (TEA 300 μM and 1 mM), iberiotoxin (150 nM) and 4‐aminopyridine (4‐AP 1 mM) increased the frequency of slow wave discharge. Apamin (1–200 nM) and glibenclamide (1 μM) had no effect on slow wave activity. Lemakalim (1 μM) and PCO‐400 (1 μM) abolished the slow waves, as did sodium nitroprusside (SNP 10 μM) and calcitonin gene‐related peptide (CGRP 100 nM). The inhibitory effect of these agents was independent of a significant change in membrane potential. In the presence of 4‐AP (1 mM), TEA (1 mM) or glibenclamide (1 μM) the inhibitory actions of SNP (10 μM) were attenuated. The inhibitory actions of CGRP (100 nM) were also reversed by glibenclamide (1 μM). In contrast, isoprenaline (1 μM) did not alter the frequency of slow wave discharge. Conclusions and implications: These results demonstrate that BKCa and 4‐AP‐sensitive K+ channels regulate the frequency of prostatic slow wave discharge. SNP and CGRP abolish slow waves in a hyperpolarisation‐independent manner, partially via opening of KATP channels. BKCa and 4‐AP‐sensitive K+ channels also play an important role in the SNP‐induced inhibition of slow wave activity. The lack of membrane hyperpolarisation associated with the SNP‐ and CGRP‐induced inhibition implies that the channels involved in this action are not predominantly located on the smooth muscle cells. British Journal of Pharmacology (2007) 151, 828–836; doi:10.1038/sj.bjp.0707283