Key result
In gallbladder smooth muscle, IP3 receptors and ryanodine receptors are spatially separated, as Ca2+ release via these pathways leads to opposite responses (contraction vs relaxation).
In gallbladder smooth muscle, IP3 receptors and ryanodine receptors appear to be spatially separated, as Ca2+ release via these pathways leads to opposite contractile responses.
May inform gallbladder motility mechanisms; leaves open translation to human biliary disorders.
The existence of functionally distinct intracellular Ca 2+ stores has been proposed in some types of smooth muscle. In this study, we sought to examine Ca 2+ stores in the gallbladder by measuring intracellular Ca 2+ concentration ([Ca 2+ ] i ) in fura 2-loaded isolated myocytes, membrane potential in intact smooth muscle, and isometric contractions in whole mount preparations. Exposure of isolated myocytes to 10 nM CCK caused a transient elevation in [Ca 2+ ] i that persisted in Ca 2+ -free medium and was inhibited by 2-aminoethoxydiphenylborane (2-APB). Application of caffeine induced a rapid spike-like elevation in [Ca 2+ ] i that was insensitive to 2-APB but was abolished by pretreatment with 10 μM ryanodine. These data support the idea that both inositol trisphosphate (IP 3 ) receptors (IP 3 R) and ryanodine receptors (RyR) are present in this tissue. When caffeine was applied in Ca 2+ -free solution, the [Ca 2+ ] i transients decreased as the interval between Ca 2+ removal and caffeine application was increased, indicating a possible leakage of Ca 2+ in these stores. The refilling of caffeine-sensitive stores involved sarcoendoplasmic reticulum Ca 2+ -ATPase activation, similar to IP 3 -sensitive stores. The moderate Ca 2+ elevation caused by CCK was associated with a gallbladder contraction, but caffeine or ryanodine failed to induce gallbladder contraction. Nevertheless, caffeine caused a concentration-dependent relaxation in gallbladder strips either under resting tone conditions or precontracted with 1 μM CCK. Taken together, these results suggest that, in gallbladder smooth muscle, multiple pharmacologically distinct Ca 2+ pools do not exist, but IP 3 R and RyR must be spatially separated because Ca 2+ release via these pathways leads to opposite responses.
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Morales et al. (2004) studied Gallbladder smooth muscle physiology. CCK, caffeine, ryanodine, 2-APB was evaluated on Intracellular Ca2+ concentration, membrane potential, and isometric contractions. In gallbladder smooth muscle, IP3 receptors and ryanodine receptors are spatially separated, as Ca2+ release via these pathways leads to opposite responses (contraction vs relaxation).
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