Membrane depolarization causes a direct activation of G protein-coupled receptors leading to local Ca 2+ release in smooth muscle
Membrane depolarization activates voltage-dependent Ca 2+ channels (VDCCs) inducing Ca 2+ release via ryanodine receptors (RyRs), which is obligatory for skeletal and cardiac muscle contraction and other physiological responses. However, depolarization-induced Ca 2+ release and its functional import...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2009-07, Vol.106 (27), p.11418-11423 |
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Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Membrane depolarization activates voltage-dependent Ca
2+
channels (VDCCs) inducing Ca
2+
release via ryanodine receptors (RyRs), which is obligatory for skeletal and cardiac muscle contraction and other physiological responses. However, depolarization-induced Ca
2+
release and its functional importance as well as underlying signaling mechanisms in smooth muscle cells (SMCs) are largely unknown. Here we report that membrane depolarization can induce RyR-mediated local Ca
2+
release, leading to a significant increase in the activity of Ca
2+
sparks and contraction in airway SMCs. The increased Ca
2+
sparks are independent of VDCCs and the associated extracellular Ca
2+
influx. This format of local Ca
2+
release results from a direct activation of G protein-coupled, M
3
muscarinic receptors in the absence of exogenous agonists, which causes activation of Gq proteins and phospholipase C, and generation of inositol 1,4,5-triphosphate (IP
3
), inducing initial Ca
2+
release through IP
3
receptors and then further Ca
2+
release via RyR2 due to a local Ca
2+
-induced Ca
2+
release process. These findings demonstrate an important mechanism for Ca
2+
signaling and attendant physiological function in SMCs. |
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ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.0813307106 |