Using Caveolin-1 Knockout Mouse to Study Impaired Detrusor Contractility and Disrupted Muscarinic Activity in the Aging Bladder

Objectives: The caveolin-1 knockout mouse has been proposed as an animal model to study impaired bladder contractility and detrusor overactivity. This study investigated the effects of aging on detrusor contraction in wild type and caveolin-1 knockout mice. Methods: Young (3-month-old) and old (1-year-old) male caveolin-1 knockout mice and their age-matched male wild type littermates (controls) were used. Longitudinal bladder strips were stimulated electrically (20 Hz) and pharmacologically using 1 to 10 μM carbachol (a nonsubtype selective cholinergic receptor agonist), 10 μM α,β-methylene adenosine triphosphate (a purinergic receptor agonist), and 100 mM potassium (a depolarizing agent). Isometric bladder strip contractions were compared between the young wild type and knockout groups and between the old wild type and knockout groups. Results: The bladder strips from the 1-year-old knockout mice exhibited a 40% to 42% decrease in electrical neural contractions and carbachol-evoked contractions compared with the 1-year-old wild type controls (P <0.05). Even though the bladder strips from the 3-month-old knockout mice demonstrated a smaller decrease (29% to 32%) in electrical neural contractions and carbachol-evoked contractions compared with their age-matched controls, the trend did not reach statistical significance (P >0.05). The postjunctional cholinergic pathway was specifically disrupted in caveolin-1 knockout animals because no difference was found in contractility between the knockout and wild type mice (young or old) when the bladders were stimulated by α,β-methylene adenosine triphosphate or potassium. The differences in cholinergic contractility between the knockout and wild type mice became significantly greater as the animals aged from 3 months old (young bladders) to 1 year old (aged bladders). Conclusions: The male caveolin-1 knockout mouse provides a much-needed animal model for the study of impaired detrusor contractility in the aging bladder.