Additional fluxes of activator Ca2+ accompanying Ca2+ release from the sarcoplasmic reticulum triggered by insP3-mobilizing agonists.
Activation of phospholipase C (PLC)-linked receptors leads not only to Ca2+ release from the sarcoplasmic reticulum (SR) by inositol-1,4,5-trisphosphate (InsP3), but also to Ca2+ entry via opening of receptor-activated Ca2+ channels (RACCs) and store-operated Ca2+ channels (SOCs), in addition to possible contributions of Ca2+ release from non-SR stores. We review recent results on these non-SR Ca2+ fluxes. In A7r5 smooth-muscle cells (SMCs), high InSP3 concentrations release Ca2+ from a thapsigargin-insensitive store. Presumably this store corresponds to the Golgi and is filled by a Pmrl-type Ca2+ pump. Molecular candidates for RACCs and SOCs are found among the members of the TRPC channel family. Inoue and colleagues have recently demonstrated that in vascular SMCs TRPC6 is an essential part of a RACC that is activated by alpha-adrenergic stimulation via the diacylglycerol branch of phosphatidylinositol-4,5-bisphosphate hydrolysis. In TRPC4 knockout mice, contractility of SMCs appears unaffected. However, endothelium-dependent relaxation is impaired mainly due to lack of a SOC activity in endothelial cells. The best-characterized SOC current, mainly observed in blood cells, is Icrac Recently, it has been proposed that CaTI (TRPV5) forms at least part of the pore of CRAC. This view is challenged by data from our laboratory.
Raeymaekers
Luc
L
Laboratorium voor Fysiologie, Katholieke Universiteit Leuven, Belgium.
Nilius
Bernd
B
Voets
Thomas
T
Missiaen
Ludwig
L
Van Baelen
Kurt
K
Vanoevelen
Jo
J
Wuytack
Frank
F
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000819:agonists / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism
D015220:Calcium Channels; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002118:Calcium