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Different effects of depolarization and muscarinic stimulation on the Ca2+/force relationship during the contraction-relaxation cycle in the guinea pig ileum

✍ Scribed by B. Himpens; R. Casteels


Publisher
Springer
Year
1990
Tongue
English
Weight
809 KB
Volume
416
Category
Article
ISSN
0031-6768

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✦ Synopsis


The effects of K + depolarization and of the muscarinic agonist carbachol on [Ca2+]i and force were investigated in smooth muscle sheets of the longitudinal layer of the ileum loaded with Fura-2. K +-rich solutions increased [Ca 2 + ]i and force to an initial peak value, which was determined by the concentration of [K+]o. Thereafter, [Ca2+]i and force declined to a lower maintained level. The Ca 2 +/force relationship observed during this contraction-relaxation cycle is represented by a clockwise hysteresis loop. At 140 mM [K+]o, this loop consisted of three components while at lower [K +]o a two-component loop was observed. The stimulation with 0.1 mM carbachol resulted in a transient increase of [Ca2+]i and force followed by a continuous decline of these parameters despite the presence of the drug. Its ECso of relaxation was around 270 nM [Ca2+]i. The CaZ+/force relationship proceeded along a counterclockwise hysteresis loop during the contraction-relaxation cycle. The extent of this loop decreased but remained unaltered in its direction during repeated stimulation with carbachol. These results suggest that (a) both agonists increase force and [Ca2+]i during stimulation; (b) during depolarization with K +, desensitization to Ca z+ occurs resulting in a clockwise hysteresis loop; (c) during carbachol stimulation, a counterclockwise hysteresis is observed. This could be due to an increased sensitivity to Ca z + mainly in tonic smooth muscle. These observations might be explained by a modulation of the Ca 2 + sensitivity by sensitizing and desensitizing mechanisms. These modulations during different stimuli could be due to different myosin light-chain kinase / myosin light-chain phosphatase ratios.