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]

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

Alberto del Valle-Rodríguez, José López-Barneo, and Juan Ureña (1 September 2003)
EMBO J. 22 (17), 4337. [DOI: 10.1093/emboj/cdg432]
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