title: Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology.
abstract: The physiological functions of the urinary bladder are to store and periodically expel urine. These tasks are facilitated by the contraction and relaxation of the urinary bladder smooth muscle (UBSM), also known as detrusor smooth muscle, which comprises the bladder wall. The large-conductance voltage- and Ca(2+)-activated K(+) (BK, BKCa, MaxiK, Slo1, or KCa1.1) channel is highly expressed in UBSM and is arguably the most important physiologically relevant K(+) channel that regulates UBSM function. Its significance arises from the fact that the BK channel is the only K(+) channel that is activated by increases in both voltage and intracellular Ca(2+). The BK channels control UBSM excitability and contractility by maintaining the resting membrane potential and shaping the repolarization phase of the spontaneous action potentials that determine UBSM spontaneous rhythmic contractility. In UBSM, these channels have complex regulatory mechanisms involving integrated intracellular Ca(2+) signals, protein kinases, phosphodiesterases, and close functional interactions with muscarinic and β-adrenergic receptors. BK channel dysfunction is implicated in some forms of bladder pathologies, such as detrusor overactivity, and related overactive bladder. This review article summarizes the current state of knowledge of the functional role of UBSM BK channels under normal and pathophysiological conditions and provides new insight toward the BK channels as targets for pharmacological or genetic control of UBSM function. Modulation of UBSM BK channels can occur by directly or indirectly targeting their regulatory mechanisms, which has the potential to provide novel therapeutic approaches for bladder dysfunction, such as overactive bladder and detrusor underactivity.
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, South Carolina petkov@cop.sc.edu.
authors.forename: Georgi V
authors.initials: GV
authors.lastname: Petkov
mesh_terms: D000200:Action Potentials; D000818:Animals; D020013:Calcium Signaling; D006801:Humans; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000819:agonists / Q000378:metabolism*; D009119:Muscle Contraction; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D014563:Urodynamics
chemical_list: C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
keywords: KCa1.1 channel; detrusor; iberiotoxin; muscarinic receptors; overactive bladder; paxilline; β-adrenergic receptors