DIFFERENTIAL ROLES OF RYANODINE- AND THAPSIGARGIN-SENSITIVE INTRACELLULAR Ca²⁺ STORES IN EXCITATION–CONTRACTION COUPLING IN SMOOTH MUSCLE OF GUINEA-PIG TAENIA CAECI

To explore roles of intracellular Ca²⁺ stores in excitation–contraction coupling in smooth muscle, we examined the effects of ryanodine, a fixer of ryanodine receptor–Ca²⁺ channels to an open state, and thapsigargin, a selective inhibitor of the Ca²⁺ pump in the intracellular stores, on smooth muscle contraction in the presence and absence of extracellular Ca²⁺ in guinea-pig taenia caeci.

In Ca²⁺-free solution, contractions induced by 0.1 mmol/L carbachol and 0.1 mmol/L histamine were reduced to approximately 65% of control by either 1 µmol/L thapsigargin or 10 µmol/L ryanodine. In contrast, caffeine-induced contraction was reduced to approximately 40% of control by ryanodine, but was not affected by thapsigargin.

In the presence of extracellular Ca²⁺, thapsigargin slowly induced a large and sustained contraction. In contrast, ryanodine did not induce an apparent contraction, but increased the sensitivity of contractile responses to receptor agonists (carbachol, AHR-602 and histamine) or depolarizing high K⁺ with no changes in the maximal contraction.

These results suggest that there are pharmacological and physiological differences between ryanodine- and thapsigargin-sensitive intracellular Ca²⁺ stores in excitation–contraction coupling in smooth muscle, which may be responsible for their differential effects on the Ca²⁺-influx pathway.