Figure 1.. (A) Isolated mesenteric artery smooth muscle cell (VSMC). (B) Ca2+ fluorescence image of a Fluo-4-AM–loaded mesenteric VSMC. (C) Ca2+ fluorescence image of the same cell as in B during the occurrence of an elementary Ca2+ release event (Ca2+ spark). The Ca2+ fluorescence images were recorded with an inverted microscope (Nikon Eclipse Ti, oil immersion objective x40, numerical aperture 1.3). Details are as described in [6]. Magnification in A (10x ocular, 20x objective, numerical aperture 0.45). Bar, 2 µm.
Figure 2.. Control of calcium sparks by voltage-dependent calcium channels. (A) Ca2+ entry from extracellular space is not required for calcium release in skeletal muscle. Charge movement within L-type channel Cav1.1 activates RyR1 channel via a direct physical interaction. Ca2+ efflux from SR through the opened RyR1 channel activates nearby RyR (RyR1 and RyR3) channels via calcium-induced calcium release (CICR). (B) In cardiomyocytes Cav1.2 mediates influx of extracellular Ca2+ into cytosol. Ca2+ then binds to and activates RyR2 channels via CICR. (C) Triggering of Ca2+ sparks is not controlled by rapid, direct cross-talk between Cav1.2 channels and RyR2 in arterial smooth muscle in contrast to cardiac and skeletal muscle cells. Instead, Cav1.2 channels contribute to global cytosolic [Ca2+], which in turn influences luminal SR calcium and thus calcium sparks. SERCA: sarco/endoplasmic reticulum calcium ATPase, BK: big conductance calcium-activated K+ channel. Modified from [29].
Figure 3.. Ca2+ sparks in wild-type and smooth muscle myosin heavy chain (SMMHC)–Ryr2−/- tibial artery smooth muscle cells (SMCs). (A) Ca2+ fluorescence image of a Fluo-4-AM–loaded control SMC. (B) Ca2+ fluorescence image of the same cell as in A during the occurrence of a Ca2+ spark. Two-dimensional images were recorded at a rate of 5/s using an inverted microscope (Nikon Eclipse Ti, oil immersion objective x40, numerical aperture 1.3;) as described in [6]. (C) Time course of Ca2+ fluorescence changes in cellular regions of interest (ROIs) without sparks (ROI a, left) and with sparks (ROI b, right). (D) Time course of Ca2+ fluorescence changes in an ROI (similar size as that in A) of a SMMHC-Ryr2−/- SMC. (E) Percentage of SMCs with Ca2+ sparks. (F) Ca2+ spark frequencies in SMCs from control and SMMHC-Ryr2−/- mice. F/F0, fluorescence/background fluorescence. Bar, 2 µm. *P < 0.05. Modified from [6].
Figure 4.. Proposed model of the role of Cav1.2 and Cav3.2 channels in arterial smooth muscle Ca2+ spark generation. Ca2+ sparks are produced by opening of clustered ryanodine receptors (RyR2) in the SR, which produces a negative-feedback effect on vasoconstriction. This vasodilatory effect is mediated by activation of large-conductance Ca2+-activated K+ (BKCa) channels, which results in hyperpolarization of VSMCs and reduced global cytosolic [Ca2+]. The majority (~70-80%) of Ca2+ sparks are triggered by Cav1.2 channels contributing to global cytosolic [Ca2+], which in turn influences luminal SR calcium via SERCA [3,104]. Cav3.2 T-type channels contribute to a minor extent [5]. SERCA, calcium pump; SR, sarcoplasmic reticulum; VSMC, mesenteric artery vascular smooth muscle cell.
We only have this paper's title and publication details.
3.2), particularly in caveolar microdomains.
No takes yet. Share an insight, caveat, or question.
Fan et al. (2019) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: