Ca2+ marks: Miniature calcium signals in single mitochondria driven by ryanodine receptors

AUTOR(ES)

Pacher, Pál

FONTE

The National Academy of Sciences

RESUMO

Propagation of cytosolic [Ca2+] ([Ca2+]c) signals to the mitochondria is believed to be supported by a local communication between Ca2+ release channels and adjacent mitochondrial Ca2+ uptake sites, but the signaling machinery has not been explored at the level of elementary Ca2+ release events. Here, we demonstrate that [Ca2+]c sparks mediated by ryanodine receptors are competent to elicit miniature mitochondrial matrix [Ca2+] signals that we call “Ca2+ marks.” Ca2+ marks are restricted to single mitochondria and typically last less than 500 ms. The decay of Ca2+ marks relies on extrusion of Ca2+ from the mitochondria through the Ca2+ exchanger, whereas [Ca2+]c sparks decline primarily by diffusion. Mitochondria also appear to have a direct effect on the properties of [Ca2+]c sparks, because inhibition of mitochondrial Ca2+ uptake results in an increase in the frequency and duration of [Ca2+]c sparks. Thus, a short-lasting opening of a cluster of Ca2+ release channels can yield activation of mitochondrial Ca2+ uptake, and the competency of mitochondrial Ca2+ handling may be an important determinant of cardiac excitability through local feedback control of elementary [Ca2+]c signals.

Documentos Relacionados

• Intra-sarcoplasmic reticulum Ca2+ oscillations are driven by dynamic regulation of ryanodine receptor function by luminal Ca2+ in cardiomyocytes
• Chloride-dependent sarcoplasmic reticulum Ca2+ release correlates with increased Ca2+ activation of ryanodine receptors.
• Functional coupling of Ca2+ channels and ryanodine receptors in cardiac myocytes.
• Termination of Ca2+ release by a local inactivation of ryanodine receptors in cardiac myocytes
• Ryanodine sensitizes the cardiac Ca2+ release channel (ryanodine receptor isoform 2) to Ca2+ activation and dissociates as the channel is closed by Ca2+ depletion