Research ArticleCalcium signaling

TRPML1 channels initiate Ca2+ sparks in vascular smooth muscle cells

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Science Signaling  23 Jun 2020:
Vol. 13, Issue 637, eaba1015
DOI: 10.1126/scisignal.aba1015

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Lighting a spark from the lysosome

Ca2+ sparks in vascular smooth muscle cells are critical for blood vessel dilation and for blood pressure regulation. Thakore et al. showed that these Ca2+ sparks were initiated by Ca2+ released from lysosomes through the cation channel TRPML1 (see the Focus by Nieves-Cintron et al.). Lysosomes in contractile vascular smooth muscle cells were immobile and localized in close proximity to an ion channel that is part of the Ca2+ spark-generating pathway, whereas they were highly mobile in proliferative vascular smooth muscle cells (as is typical for most cell types). Vascular smooth muscle cells from mice deficient in TRPML1 did not generate Ca2+ sparks, and these mice were spontaneously hypertensive. Thus, TRPML1 generates the signal that initiates Ca2+ sparks to relax vascular smooth muscle and modulate blood pressure.

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