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.

Quercetin relaxes rat tail main artery partly via a PKG‐mediated stimulation of KCa1.1 channels

“…In fact, the additional increase in vessel tone subsequent to the block of K Ca 1.1 channels with iberiotoxin was not affected by the presence of ryanodine, thus indicating that K Ca 1.1 channels remain active even when Ca 2+ release from SR is blocked (Szado et al . ). This might be due to methoxamine, because α 1 adrenergic activation has been shown to decrease the frequency of Ca 2+ sparks through a PKC‐mediated inhibition of ryanodine receptors (Mauban et al .…”

In the presence of L‐NAME SERCA blockade induces endothelium‐dependent contraction of mouse aorta through activation of smooth muscle prostaglandin H2/thromboxane A2 receptors

“…CPA also inhibits SERCA in the smooth muscle SR, which belongs predominantly to the type 2b isoform (Wu et al ., 2001), but the contractile consequences of this action appear only at higher concentrations. We have recently shown that the concentration of CPA required to maximally block refilling of vascular smooth muscle SR is 30 μ M (Szado et al ., 2001). At this concentration CPA‐induced tonic contractions are dependent on Ca 2+ entry through SOC, which is supported by the fact that this contraction is inhibited by SKF 96365 and 2APB (Figure 6).…”

EDHF and Gap Junctions: Important Regulators of Vascular Tone Within the Microcirculation

“…For example, smooth muscle activation is often associated with depolarization which leads to an activation of K + -channels in the smooth muscle membrane especially BK Ca acting as a negative feedback mechanism [91,92]. BK Ca are activated either by localized elevations of [Ca 2+ ] i ('Ca 2+ sparks'), by a depolarization of the smooth muscle membrane due to their voltage dependency or by other means [93,94]. Thus, BK Ca activity depends on the activation state of the smooth muscle which varies depending on the type of experimental setup and preconstriction level of the vessels studied.…”