Cyclopiazonic acid, an inhibitor of Ca2+‐ATPase in sarcoplasmic reticulum, increases excitability in ileal smooth muscle
Y Uyama, Y Imaizumi… - British journal of …, 1993 - Wiley Online Library
Y Uyama, Y Imaizumi, M Watanabe
British journal of pharmacology, 1993•Wiley Online Library1 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 …
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 …
- 1Effects 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.
- 2After 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.
- 3Spontaneous 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.
- 4Application 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.
- 5The 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.
- 6These 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.
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