title: Role of sarcoplasmic reticulum in regulation of tonic contraction of rabbit basilar artery.
abstract: Superficial sarcoplasmic reticulum (SR) regulates smooth muscle force development directly by Ca(2+) release and removal to and from the cytoplasm (Somlyo and Somlyo. J Cardiovasc Pharmacol 8, Suppl 8: S42-S47, 1986) by buffering Ca(2+) influx and contributing to Ca(2+) extrusion (Mueller and van Breemen. Nature 281: 682-683, 1979) and indirectly by releasing Ca(2+) near Ca(2+)-activated K(+) channels (K(Ca)) 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 K(Ca) were evaluated by measuring force and intracellular Ca(2+) concentration ([Ca(2+)](i)) in response to the SR-depleting agents thapsigargin and ryanodine and the large conductance K(Ca) (BK(Ca)) blockers iberiotoxin (IbTX) and tetraethylammonium ion (TEA). A large contraction was observed in response to K(Ca) blockade with either 3 mM TEA or 100 nM IbTX and also after addition of 10 microM ryanodine or 2 microM thapsigargin. When K(Ca) 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 [Ca(2+)](i) in response to sequential blockade of sarco(endo)plasmic reticulum Ca(2+)-ATPase and K(Ca) regardless of the order of application. It appears that a significant fraction of K(Ca) remains activated in the absence of SR function and that SR contributes to relaxation after blockade of K(Ca). We found that depletion of SR before stimulating Ca(2+) influx through voltage-gated Ca(2+) 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.
authors.affiliation: Vancouver Vascular Biology Research Center and Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
authors.forename: T
authors.initials: T
authors.lastname: Szado
authors.forename: M
authors.initials: M
authors.lastname: McLarnon
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: C
authors.initials: C
authors.lastname: van Breemen
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology*; D002021:Buffers; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D002021:Buffers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012433:Ryanodine; D019789:Tetraethylammonium; D019284:Thapsigargin; C064719:iberiotoxin; D002118:Calcium