Age-related changes in gallbladder contractility and cytoplasmic Ca²⁺ concentration in the guinea pig

Gallbladder (GB) motility diminishes with aging. This study was performed to characterize mechanisms that are involved in changes in GB contractility that occur during aging. Cytoplasmic Ca²⁺ concentrations ([Ca²⁺](i)) and the contractile force of guinea pig GB muscle strips were simultaneously measured using fura-2 and force-displacement transducers. The binding ability of the Ca²⁺ channel antagonist and GB muscle compliance were also examined. The COOH-terminal octapeptide of cholecystokinin (CCK-8) evoked a dose- dependent increase in force and [Ca²⁺](i). Changes of [Ca²⁺](i) and contractile force of muscle strips in response to CCK-8 were significantly greater in young (2 mo old) compared with mature and aged (12 and 24 mo old) guinea pigs (changes in [Ca²⁺](i), ED₅₀: 46.1 nM at 2 mo, 6.1 μM at 12 mo, and 2.8 mM at 24 mo; changes of contractile force, ED₅₀: 24.8 μM at 2 mo, 2.1 mM at 12 mo, and 357 mM at 24 mo). However, the magnitude of the contraction at each percent change in [Ca²⁺](i) was actually similar in young and aged guinea pigs. In a Ca²⁺-free buffer, the responses of [Ca²⁺](i) and force to CCK-8 in both young and aged GB muscles decreased, but those were still dose and age dependent. Binding ability of the Ca²⁺ channel antagonist did not differ in the young and aged groups, but the compliance of the GB muscle strip decreased with aging. These results suggest that both a reduced mobilization of intracellular Ca²⁺ and a decreased muscle compliance are responsible, at least in part, for age-related reduced contraction of guinea pig GB in response to CCK.