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Spontaneous phasic activity of the pig urinary bladder smooth muscle: characteristics and sensitivity to potassium channel modulators
Author(s) -
Buckner Steven A,
Milicic Ivan,
Daza Anthony V,
Coghlan Michael J,
Gopalakrishnan Murali
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704499
Subject(s) - iberiotoxin , chemistry , contraction (grammar) , ryanodine receptor , apamin , medicine , endocrinology , muscle contraction , nifedipine , myogenic contraction , bk channel , potassium channel blocker , potassium channel , calcium , voltage dependent calcium channel , smooth muscle
A hallmark for unstable bladder contractions is hyperexcitability and changes in the nature of spontaneous phasic activity of the bladder smooth muscle. In this study, we have characterized the spontaneous activity of the urinary bladder smooth muscle from the pig, a widely used model for studying human bladder function. Our studies demonstrate that phasic activity of the pig detrusor is myogenic and is influenced by the presence of urothelium. Denuded strips exhibit robust spontaneous activity measured as mean area under the contraction curve (AUC=188.9±15.63 mNs) compared to intact strips (AUC=7.3±1.94 mNs). Spontaneous phasic activity, particularly the amplitude, is dependent on both calcium entry through voltage‐dependent calcium channels and release from ryanodine receptors as shown by inhibition of spontaneous activity by nifedipine and ryanodine respectively. Inhibition of BK Ca channels by iberiotoxin (100 n M ) resulted in an increase in contraction amplitude (89.1±20.4%) and frequency (92.5±31.0%). The SK Ca channel blocker apamin (100 n M ) also increased contraction amplitude (69.1±24.3%) and frequency (53.5±13.6%) demonstrating that these mechanisms are critical to the regulation of phasic spontaneous activity. Inhibition of K ATP channels by glyburide (10 μ M ) did not significantly alter myogenic contractions (AUC=18.5±12.3%). However, K ATP channel openers (KCOs) showed an exquisite sensitivity for suppression of spontaneous myogenic activity. KCOs were generally 15 fold more potent in suppressing spontaneous activity compared to contractions evoked by electrical field‐stimulation. These studies suggest that potassium channel modulation, particularly K ATP channels, may offer a unique mechanism for controlling spontaneous myogenic activity especially those associated with the hyperexcitability occurring in unstable bladders.British Journal of Pharmacology (2002) 135 , 639–648; doi: 10.1038/sj.bjp.0704499