The local control of cytosolic Ca2+ as a propagator of CNS communication--integration of mitochondrial transport mechanisms and cellular responses.
Ca2+ signals propagate in wave form along individual cells of the central nervous system (CNS) and through networks of connected cells of neuronal and multiple glial cell types. In order for wave fronts to convey information, signaling mechanisms are required that allow waves to propagate reproducibly and without decrement in signal strength over long distances. CNS Ca2+ waves are under specific integrated local control, made possible by interactions at local subcellular microdomains between endoplasmic reticulum and mitochondria. Active mitochondria located near the mouth of inositol trisphosphate receptor (InsP3R) channel clusters in glia take up Ca2+, which may prevent a buildup of Ca2+ around the InsP3R channel, thereby decreasing the rate of Ca2+-induced receptor inactivation, and prolonging channel open time. Mitochondria may amplify InsP3-dependent Ca2+ signals by a transient permeability transition in response to Ca2+ uptake into the mitochondrion. Other evidence suggests privileged access into mitochondria for Ca2+ entering neurons by glutamatergic receptor channels. This enables specific signal modulation as the Ca2+ wave is propagated into neurons, such that mitochondria located close to glutamate channels can prolong the neuronal cytosolic response time by successive uptake and release of Ca2+. Disruption of mitochondrial function deregulates the ability of CNS-derived cells to undergo normal Ca2+ signaling and wave propagation.
Simpson
P B
PB
Department of Pharmacology, Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Harlow, Essex, United Kingdom. peter_simpson@merck.com
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002490:Central Nervous System / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*
D002118:Calcium