Membrane depolarization causes a direct activation of G protein-coupled receptors leading to local Ca2+ 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 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.
Liu
Qing-Hua
QH
Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, USA.
Zheng
Yun-Min
YM
Korde
Amit S
AS
Yadav
Vishal R
VR
Rathore
Rakesh
R
Wess
Jürgen
J
Wang
Yong-Xiao
YX
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism
D015220:Calcium Channels; D043562:Receptors, G-Protein-Coupled; D019837:Ryanodine Receptor Calcium Release Channel; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D011188:Potassium; D002118:Calcium