@article{APS6626,
author = {Timo Kirschstein and Mirko Rehberg and Rika Bajorat and Tursonjan Tokay and Katrin Porath and Rüdiger Köhling},
title = {High K+-induced contraction requires depolarization-induced Ca2+ release from internal stores in rat gut smooth muscle},
journal = {Acta Pharmacologica Sinica},
volume = {30},
number = {8},
year = {2016},
keywords = {},
abstract = {Aim: Depolarization-induced contraction of smooth muscle is thought to be mediated by Ca2+ influx through voltage-gated L-type Ca2+ channels. We describe a novel contraction mechanism that is independent of Ca2+ entry.
Methods: Pharmacological experiments were carried out on isolated rat gut longitudinal smooth muscle preparations, measuring isometric contraction strength upon high K+-induced depolarization.
Results: Treatment with verapamil, which presumably leads to a conformational change in the channel, completely abolished K+-induced contraction, while residual contraction still occurred when Ca2+ entry was blocked with Cd2+. These results were further confirmed by measuring intracellular Ca2+ transients using Fura-2. Co-application of Cd2+ and the ryanodine receptor blocker DHBP further reduced contraction, albeit incompletely. Additional blockage of either phospholipase C (U 73122) or inositol 1,4,5-trisphophate (IP3) receptors (2-APB) abolished most contractions, while sole application of these blockers and Cd2+ (without parallel ryanodine receptor manipulation) also resulted in incomplete contraction block.
Conclusion: We conclude that there are parallel mechanisms of depolarization-induced smooth muscle contraction via (a) Ca2+ entry and (b) Ca2+ entry-independent, depolarization-induced Ca2+-release through ryanodine receptors and IP3, with the latter being dependent on phospholipase C activation.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/6626}
}