Channeling Calcium Signals

Sci. STKE, 9 September 2003
Vol. 2003, Issue 199, p. tw345-TW345
DOI: 10.1126/stke.2003.199.tw345
Calcium

Channeling Calcium Signals

Del Valle-Rodríguez et al. showed that plasma membrane voltage-gated calcium (Ca2+) channels can mediate vascular smooth muscle cell (VSMCs) contraction by a mechanism that is independent of their function as pores that allow entry of extracellular Ca2+ into the cell. Rather, the channels appear to trigger an indirect pathway that leads to the release of Ca2+ from the sarcoplasmic reticulum (SR). VSMCs, which regulate blood pressure and blood flow, contract in response to increases in intracellular calcium concentration ([Ca2+]i) that follow Ca2+ influx through voltage-gated channels in the plasma membrane or receptor-mediated release of Ca2+ from stores in the SR. In cultured rat basilar artery myocytes loaded with Ca2+ indicators, membrane depolarization under voltage clamp or in response to elevated extracellular K+ elicited contractions, as well as a rapid increase in [Ca2+]i in Ca2+-free medium (no added Ca2+ plus a chelator). The graded, depolarization-dependent increase in [Ca2+]i was potentiated by L-type Ca2+ channel agonists and inhibited by organic antagonists that alter gating but not by cadmium or nickel (which block Ca2+ flux through the open channel). Pharmacological analysis indicated that this increase in [Ca2+]i was secondary to Ca2+ release from the SR and depended on a pathway that involved heterotrimeric GTP-binding proteins (G proteins), phospholipase C (PLC), inositol trisphosphate (IP3), and ryanodine receptors. Thus, the voltage-dependent gating of Ca2+ channels in VSMCs appears somehow to stimulate G proteins and thereby to activate a signaling pathway that results in the release of Ca2+ from the SR.

A. del Valle-Rodríguez, J. López-Barneo, J. Ureña, Ca2+ channel-sarcoplasmic reticulum coupling: A mechanism of arterial myocyte contraction without Ca2+ influx. EMBO J. 22, 4337-4345 (2003). [Abstract] [Full Text]

Citation:

Channeling Calcium Signals. Sci. STKE 2003, tw345-TW345 (2003).
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882