Effects of potassium channel modulators on human detrusor smooth muscle myogenic phasic contractile activity: Potential therapeutic targets for overactive bladder

• Published in: Urology (Ridgewood, N.J.) N.J.), 2006-08, Vol.68 (2), p.442-448
• Main Authors: Darblade, Benoît, Behr-Roussel, Delphine, Oger, Stéphanie, Hieble, Jean-Paul, Lebret, Thierry, Gorny, Diane, Benoit, Gérard, Alexandre, Laurent, Giuliano, François
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Calcium Channels, L-Type - drug effects; Calcium Channels, L-Type - physiology; Humans; In Vitro Techniques; Medical sciences; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Nephrology. Urinary tract diseases; Potassium Channels - drug effects; Potassium Channels - physiology; Urinary Bladder - drug effects; Urinary Bladder - physiology; Urinary Incontinence - drug therapy; Urinary Incontinence - physiopathology; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/j.urology.2006.03.039

Increased urinary bladder detrusor smooth muscle phasic contractility has been suggested to be associated with idiopathic bladder overactivity (OAB). We examined the role of voltage-dependent l-type calcium channels, adenosine triphosphate-sensitive potassium (K ATP) channels, and calcium-activated potassium (BK Ca and SK Ca) channels in the regulation of human detrusor phasic contractile activity. Isolated human bladder strip phasic contractions were measured and quantified as the mean area under the force-time curve, amplitude, and frequency of phasic contractions in 22 bladder samples. Human detrusor strips displayed myogenic phasic contractions in the presence of atropine (10 −6 M), phentolamine (10 −6 M), propranolol (10 −6 M), suramin (10 −5 M), and tetrodotoxin (10 −6 M). The l-type calcium channel inhibitor nifedipine (300 nM) abolished the contractile activity. Blockade of K ATP channels by glibenclamide (1 and 10 μM) did not alter myogenic contractions. In contrast, the K ATP channel opener pinacidil (10 μM) markedly inhibited phasic contractility. Iberiotoxin (100 nM) and apamin (100 nM), potent and selective inhibitors of BK Ca and SK Ca channels, respectively, significantly increased the area under the force-time curve and the amplitude of contractions. Phasic contractions of human detrusor are dependent on calcium entry through l-type calcium channels. BK Ca and SK Ca channels play a key role in the modulation of human detrusor smooth muscle phasic contractility. Furthermore, these observations support the concept that increasing conductance through K ATP, BK Ca, and SK Ca channels may represent attractive pharmacologic targets for decreasing phasic contractions of detrusor smooth muscle in OAB.