Effects of anoxia and aglycaemia on cytosolic calcium regulation in rat sensory neurons
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چکیده
Running head : Effects of anoxia and aglycaemia on neuronal [Ca 2+ ] i. ABSTRACT Nociceptive neurons play an important role in ischemia by sensing and transmitting information to the CNS and by secreting peptides and nitric oxide which can have local effects. Whilst these responses are probably primarily mediated by acid sensing channels other events occurring in ischemia may also influence neuron function. In this study we have investigated the effects of anoxia and anoxic aglycaemia on Ca 2+ regulation in sensory neurons from rat dorsal root ganglia. Anoxia increased [Ca 2+ ] i by evoking Ca 2+ release from two distinct internal stores one sensitive to FCCP and one sensitive to caffeine, CPA and ryanodine (assumed to be the endoplasmic reticulum (ER)). Anoxia also promoted progressive decline in ER Ca 2+ content. Despite partially depolarising mitochondria, anoxia had relatively little effect upon mitochondrial Ca 2+ uptake when neurons were depolarised but substantively delayed mitochondrial Ca 2+ release and subsequent Ca 2+ clearance from the cytosol upon repolarisation. Anoxia also reduced both SERCA activity and Ca 2+ extrusion (probably via PMCA). Thus anoxia has multiple effects upon [Ca 2+ ] i homeostasis in sensory neurons involving internal stores, mitochondrial buffering, and Ca 2+ pumps. Under conditions of anoxic aglycaemia there was a biphasic and more profound elevation of [Ca 2+ ] i which was associated with complete ER Ca 2+ store emptying and progressive, and eventually complete, inhibition of Ca 2+ clearance by PMCA and SERCA. These data clearly show that loss of oxygen, and exhaustion of glycolytic substrates, can profoundly affect many aspects of cell Ca 2+ regulation and this may play an important role in modulating neuronal responses to ischemia.
منابع مشابه
Effects of Anoxia and Aglycemia on Cytosolic Calcium Regulation in Rat Sensory Neurons
Nociceptive neurons play an important role in ischemia by sensing and transmitting information to the CNS and by secreting peptides and nitric oxide, which can have local effects. While these responses are probably primarily mediated by acid sensing channels, other events occurring in ischemia may also influence neuron function. In this study, we have investigated the effects of anoxia and anox...
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