Article

Ca2+ channel-sarcoplasmic reticulum coupling: A mechanism of arterial myocyte contraction without Ca2+ influx

Laboratorio de Investigaciones Biomédicas, Departamento de Fisiología and Hospital Universitario Virgen del Rocío, Universidad de Sevilla, E-41013, Seville, Spain.
The EMBO Journal (Impact Factor: 10.43). 10/2003; 22(17):4337-45. DOI: 10.1093/emboj/cdg432
Source: PubMed

ABSTRACT

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.

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    • "While most vascular smooth muscle expresses all 3 known RyR isoforms (RyR1–3), it is primarily the activation of RyR1 and RyR2 that regulates excitation–contraction coupling [2]. These receptors are activated by Ca 2+ , and can act as amplifiers of smaller Ca 2+ signals caused by Ca 2+ influx or inositol 1,4,5-trisphosphate (IP 3 )-mediated Ca 2+ release [3]. This amplification, called " Ca 2+ induced Ca 2+ release " (CICR), mobilizes large amounts of SR Ca 2+ into the cytosol and has been proposed to serve an important role in excitation–contraction coupling in smooth muscle [4]. "
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    • "Values are presented as meanSEM. *P0.05, **P0.01.14,25,20We now show that in normal conditions, CCICR mediates Ca 2 release and sensitization of the contractile apparatus necessary to generate sustained VSM contractions. "
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