The dissociation constant of verapamil estimated from its effect on Ca concentration-tension curves in guinea-pig tracheal muscle
✍ Scribed by H. Gonda; K. Baba; T. Satake; K. Takagi; T. Tomita
- Publisher
- Elsevier
- Year
- 1988
- Tongue
- English
- Weight
- 502 KB
- Volume
- 1
- Category
- Article
- ISSN
- 0952-0600
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✦ Synopsis
Concentration-tension curves for calcium ions (Ca 2+) were studied in indomethacin-treated guinea-pig tracheal muscle in the presence of different concentrations of carbachol in media containing 5 .9 mM K+ or 40 mM K+ . The effect of verapamil was investigated taking into account the steepness (the Hill coefficient) of the Ca2 + curve. When carbachol (1 uM) was added to 40 mM K+ solution, the C a2 + concentration to produce half maximum tension (EC 50) was reduced from 0.2 mM to 0 .08 mM and the Hill coefficient was increased from 1 .4 to 2 .0, respectively . In the presence of carbachol (I ,uM), the Ca 2 + concentration-tension curve was not much influenced by increasing the K + concentration from 5 .9 to 40 mM K + . Verapamil (0 .5 pM) shifted the Ca 2+ concentration-tension curve to the right in a parallel manner under all experimental conditions, the shift being greater with curves having a smaller Hill coefficient. The dissociation constant of verapamil was not altered by carbachol when estimated from the shift of the curve if the Hill coefficient is taken into consideration . It is concluded that the relatively low susceptibility of carbachol-induced contractions to verapamil in the presence of 40 mM K+, compared with these produced by K + alone, is not due to a decreased verapamil affinity but to improved Ca 2 +-response coupling.