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Tonic Potentiation And Attenuation Produced By Membrane Depolarization In Guinea‐Pig Trachealis
Author(s) -
Yamaki Kenichi,
Ogawa Masahiro,
Ito Yasushi
Publication year - 2000
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2000.03247.x
Subject(s) - depolarization , verapamil , chemistry , cyclopiazonic acid , medicine , endocrinology , membrane potential , tonic (physiology) , extracellular , biophysics , calcium , intracellular , biochemistry , biology , organic chemistry
SUMMARY 1. We studied how membrane depolarization directly affected intracellular Ca 2+ signalling when voltage‐operated Ca 2+ channels (VOCC) were not available in guinea‐pig tracheal smooth muscle. To block VOCC, we used 3 μmol/L verapamil, which completely abolished high K + (20–60 mmol/L)‐induced contraction, and elevation of fura‐2 signal. 2. Muscle tone was generated by adding Ca 2+ to the extracellular Ca 2+ ‐free solution containing prostaglandin (PG)E 2 (100 nmol/L) after abolishing basal tone with indomethacin (1 μmol/L). 3. In the absence of verapamil, high K + (20–60 mmol/L) solution potentiated 2.4 mmol/L Ca 2+ ‐induced sustained contractions. Even in the presence of 3 μmol/L verapamil, replacement with 20 and 40 mmol/L K + solution induced tonic potentiation, which was changed to attenuation with a higher K + solution (60 mmol/L), lower extracellular Ca 2+ concentration ([Ca 2+ ] o ) and pretreatment with cyclopiazonic acid (10 μmol/L), a Ca 2+ sequestration inhibitor. 4. These results indicate that the balance between depolarization‐dependent Ca 2+ release and receptor‐operated cation channel inhibition may determine whether tonic potentiation or attenuation is manifested, depending on the availability of VOCC, the magnitude of the depolarization, [Ca 2+ ] o and Ca 2+ content in the sarcoplasmic reticulum.