The contribution of intracellular Ca 2+ release to contraction in human bladder smooth muscle

The importance of Ca 2+ release from the sarcoplasmic reticulum (SR) in excitation contraction (EC) coupling in human detrusor muscle remains controversial. In this paper the contribution of Ca 2+ release to agonist induced contraction is assessed. Dose response curves to carbachol (0.01–10 μ M ) were constructed before and after exposure to 200 n M Thapsigargin (Tg). Tg pre‐treatment reduced the force of contraction at all agonist concentrations however, the reduction was dose dependent. At 0.1 μ M the contractions were reduced to 14.5±7% (mean±s.e.mean) of controls ( n =8) while at 10 μ M the contractions were only reduced to 92±3% of controls ( n =10). The role of external Ca 2+ was examined by measuring the magnitude of contraction to low and high doses of agonist in the presence and absence of external Ca 2+ . With (0.1–0.3 μ M ) carbachol the contractions in nominally Ca 2+ free media were 4±4% of controls ( n =7) whilst with (1–10 μ M ) carbachol the contractions were 36±8% of controls ( n =7) suggesting that at low agonist concentrations the release of Ca 2+ has a requirement for external Ca 2+ . Pre‐treatment of muscle strips with the Ca 2+ channel blocking agent diltiazem reduced the contractile responses to carbachol. Contractions induced by 0.1 μ M were reduced to 29±11% ( P <0.05) of controls while those activated by 10 μ M were reduced to 86±6% ( P =0.1) of controls ( n =4) suggesting the Ca 2+ influx needed to activate internal store release at low agonist stimulation is through L‐type Ca 2+ channels. These observations confirm the importance of thapsigargin sensitive intracellular Ca 2+ store release in the activation of contraction of detrusor smooth muscle and suggest the overall contribution of this store depends upon the magnitude of the agonist stimulation.British Journal of Pharmacology (1999) 127 , 996–1002; doi: 10.1038/sj.bjp.0702640