Role of sarcoplasmic reticulum in regulation of tonic contraction of rabbit basilar artery

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Abstract

Superficial sarcoplasmic reticulum (SR) regulates smooth muscle force development directly by Ca2+ release and removal to and from the cytoplasm (Somlyo and Somlyo. J Cardiovasc Pharmacol 8, Suppl 8: S42-S47, 1986) by buffering Ca2+ influx and contributing to Ca2+ extrusion (Mueller and van Breemen. Nature 281: 682-683, 1979) and indirectly by releasing Ca2+ near Ca2+-activated K+ channels (KCa) to hyperpolarize the plasma membrane (Bolton and Imaizumi. Cell Calcium 20: 141-152, 1996 and Nelson et al. Science 270: 633-637, 1995). In the rabbit basilar artery, relative contributions of direct effects and those mediated through activation of KCa were evaluated by measuring force and intracellular Ca2+ concentration ([Ca2+]i) in response to the SR-depleting agents thapsigargin and ryanodine and the large conductance KCa (BKCa) blockers iberiotoxin (IbTX) and tetraethylammonium ion (TEA). A large contraction was observed in response to KCa blockade with either 3 mM TEA or 100 nM IbTX and also after addition of 10 μM ryanodine or 2 μM thapsigargin. When KCa was blocked first with TEA or IbTX, subsequent addition of thapsigargin or ryanodine also increased force. Measurements of fura 2 fluorescence showed parallel increases in [Ca2+]i in response to sequential blockade of sarco(endo)plasmic reticulum Ca2+-ATPase and KCa regardless of the order of application. It appears that a significant fraction of KCa remains activated in the absence of SR function and that SR contributes to relaxation after blockade of KCa. We found that depletion of SR before stimulating Ca2+ influx through voltage-gated Ca2+ channels markedly reduced force development rate and that thapsigargin abolished this effect. We conclude that the SR of rabbit cerebral arteries modulates constriction by direct and indirect mechanisms.

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Szado, T., McLarnon, M., Wang, X., & Van Breemen, C. (2001). Role of sarcoplasmic reticulum in regulation of tonic contraction of rabbit basilar artery. American Journal of Physiology - Heart and Circulatory Physiology, 281(4 50-4). https://doi.org/10.1152/ajpheart.2001.281.4.h1481

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