Ca2+ channel-sarcoplasmic reticulum coupling: a mechanism of arterial myocyte contraction without Ca2+ influx.
Contraction of vascular smooth muscle cells (VSMCs) depends on the rise of cytosolic [Ca2+] owing to either Ca2+ influx through voltage-gated Ca2+ channels of the plasmalemma or receptor-mediated Ca2+ release from the sarcoplasmic reticulum (SR). We show that voltage-gated Ca2+ channels in arterial myocytes mediate fast Ca2+ release from the SR and contraction without the need of Ca2+ influx. After sensing membrane depolarization, Ca2+ channels activate G proteins and the phospholipase C-inositol 1,4,5-trisphosphate (InsP3) pathway. Ca2+ released through InsP3-dependent channels of the SR activates ryanodine receptors to amplify the cytosolic Ca2+ signal. These observations demonstrate a new mechanism of signaling SR Ca(2+)-release channels and reveal an unexpected function of voltage-gated Ca2+ channels in arterial myocytes. Our findings may have therapeutic implications as the calcium-channel-induced Ca2+ release from the SR can be suppressed by Ca(2+)-channel antagonists.
del Valle-Rodríguez
Alberto
A
Laboratorio de Investigaciones Biomédicas, Departamento de Fisiología and Hospital Universitario Virgen del Rocío, Universidad de Sevilla, E-41013, Seville, Spain.
López-Barneo
José
J
Ureña
Juan
J
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008564:Membrane Potentials; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
D015220:Calcium Channels; D019837:Ryanodine Receptor Calcium Release Channel; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins