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Cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum Ca 2+ ‐pump, reduces Ca 2+ ‐dependent K + currents in guinea‐pig smooth muscle cells
Author(s) -
Suzuki Masanori,
Muraki Katsuhiko,
Imaizumi Yuji,
Watanabe Minora
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14475.x
Subject(s) - cyclopiazonic acid , chemistry , depolarization , endoplasmic reticulum , patch clamp , biophysics , membrane potential , caffeine , calcium , analytical chemistry (journal) , endocrinology , biochemistry , chromatography , biology , receptor , organic chemistry
1 Effects of cyclopiazonic acid (CPA), a specific inhibitor of the Ca 2+ ‐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. 2 Under whole‐cell clamp, CPA (1–10 μ m ) 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 μ m in ileal cells under these conditions. The current reduced by CPA recovered by more than 70% after washout. 3 The transient outward current elicited by application of 5 m m caffeine at a holding potential of — 50 mV in Ca 2+ free solution was almost abolished, when the preceding Ca 2+ ‐loading of the cell in a solution containing 2.2 m m Ca 2+ was performed in the presence of 3 μ m CPA. 4 When the Ca 2+ ‐dependent K + current ( I K‐Ca ) and Ca 2+ current ( I Ca ) were inhibited by addition of Ca 2+ , the remaining delayed rectifier type K + current was not affected by 10 μ m CPA. When outward currents were blocked by replacement of K + by Cs + in the pipette solution, the remaining I Ca was not affected by 10 μ m CPA. 5 CPA (10 μ m ) did not affect the conductance of single maxi Ca 2+ ‐dependent K + channels or the Cd 2+ ‐dependence of their open probability in both inside‐ and outside‐out configurations. 6 These results indicate that I K‐Ca is selectively and strongly suppressed by CPA. Its effects may be attributed to a decrease in Ca 2+ ‐uptake into SR, resulting in a decrease in Ca 2+ ‐induced Ca 2+ release which is triggered by Ca 2+ entering through voltage‐dependent Ca 2+ channels and therefore less activation of these K channels. 7 CPA may be extremely valuable pharmacological tool for investigating intracellular Ca 2+ mobilization and ionic currents regulated by intracellular Ca 2+ .