Effects of cyclopiazonic acid (CPA), a specific inhibitor of the Ca2+‐ATPase in sarcoplamic reticulum (SR), on membrane ionic currents were examined in single smooth muscle cells freshly isolated from ileal longitudinal strips and urinary bladder of the guinea‐pig. Under whole‐cell clamp, CPA (1–10 μm) reduced peak outward current elicited by depolarization in a concentration‐dependent manner. The concentration of CPA required for 50% decrease in the peak outward current was ∼ 3 μm in ileal cells under these conditions. The current reduced by CPA recovered by more than 70% after washout. The transient outward current elicited by application of 5 mm caffeine at a holding potential of — 50 mV in Ca2+ free solution was almost abolished, when the preceding Ca2+‐loading of the cell in a solution containing 2.2 mm Ca2+ was performed in the presence of 3 μm CPA. When the Ca2+‐dependent K+ current (IK‐Ca) and Ca2+ current (ICa) were inhibited by addition of Ca2+, the remaining delayed rectifier type K+ current was not affected by 10 μm CPA. When outward currents were blocked by replacement of K+ by Cs+ in the pipette solution, the remaining ICa was not affected by 10 μm CPA. CPA (10 μm) did not affect the conductance of single maxi Ca2+‐dependent K+ channels or the Cd2+‐dependence of their open probability in both inside‐ and outside‐out configurations.6 These results indicate that IK‐Ca is selectively and strongly suppressed by CPA. Its effects may be attributed to a decrease in Ca2+‐uptake into SR, resulting in a decrease in Ca2+‐induced Ca2+ release which is triggered by Ca2+ entering through voltage‐dependent Ca2+ channels and therefore less activation of these K channels.7 CPA may be extremely valuable pharmacological tool for investigating intracellular Ca2+ mobilization and ionic currents regulated by intracellular Ca2+.

Suzuki, M., Muraki, K., Imaizumi, Y., & Watanabe, M. (1992). Cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum Ca2+‐pump, reduces Ca2+‐dependent K+ currents in guinea‐pig smooth muscle cells. British Journal of Pharmacology, 107(1), 134–140. Portico.