{'fraction_non_alphanumeric': 0.03297199638663053, 'fraction_numerical': 0.028003613369467027, 'mean_word_length': 5.22191011235955, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Cyclopiazonic acid, an inhibitor of Ca2+‐ATPase in sarcoplasmic reticulum, increases excitability in ileal smooth muscle

1 Effects of cyclopiazonic acid (CPA), a specific inhibitor of Ca2+‐ATPase in endo‐ and sarcoplasmic reticulum (ER/SR), on contractile responses, cytosolic Ca2+ concentration and spontaneous electrical activity were examined in ileal longitudinal smooth muscle strips. 2 After intracellular stored Ca2+ in intact ileal strips was depleted by application of 25 mm caffeine in Ca2+‐free solution, Ca2+‐loading was performed in the absence or presence of 10 μm CPA in a standard solution containing 2.2 mm Ca2+. Subsequent application of caffeine in Ca2+‐free solution induced a phasic contraction which was significantly smaller in the strip pretreated with CPA than that in the control. 3 Spontaneous and 20 mm K+‐induced contractions in the presence of 1 μm atropine were markedly enhanced by 1–30 μm CPA, whereas that induced by 80 mm K+ was not. The magnitude of repetitive transient elevation of cytosolic Ca2+ concentration ([Ca2+]i) and concomitant phasic contractions were markedly enhanced by CPA. The effects were abolished by 10 μm verapamil and restored by 10 μm Bay K 8644. 4 Application of 10 μm CPA depolarized the cell by about 5 mV, decreased the action potential (AP) afterhyperpolarization and markedly increased the frequency of spontaneous AP. These effects were mimicked by 100 nm charybdotoxin. 5 The rate of decay of [Ca2+]i and tension after the bathing solution was changed from one containing 140 mm K+ and 2.2 mm Ca2+ to one containing 5.9 mm K+ and 0 mm Ca2+ was significantly slowed when 10 μm CPA was added to the latter solution. 6 These results indicate that CPA enhances ileal smooth muscle excitability and increases Ca2+‐influx through voltage‐dependent Ca2+ channels. The effect may be consistent with the hypothesis that CPA‐induced decrease in stored Ca due to Ca‐pump inhibition reduces the Ca2+‐dependent K+ current and indirectly enhances Ca2+‐influx through membrane activity resulting from the increased excitability. Direct evidence for the regulation of Ca2+ channel activity by intracellular Ca storage sites was not obtained in the present study.