Cytosolic calcium regulation in rat afferent vagal neurons during anoxia

Sensory neurons are able to detect tissue ischaemia and both transmit information to the brainstem as well as release local vasoactive mediators. Their ability to sense tissue ischaemia is assumed to be primarily mediated through proton sensing ion channels, lack of oxygen however may also affect sensory neuron function. In this study we investigated the effects of anoxia on isolated capsaicin sensitive neurons from rat nodose ganglion. Acute anoxia triggered a reversible increase in Ca²⁺]_i that was mainly due to Ca²⁺-efflux from FCCP sensitive stores and from caffeine and CPA sensitive ER stores. Prolonged anoxia resulted in complete depletion of ER Ca²⁺-stores. Mitochondria were partially depolarised by acute anoxia but mitochondrial Ca²⁺-uptake/buffering during voltage-gated Ca²⁺-influx was unaffected. The process of Ca²⁺-release from mitochondria and cytosolic Ca²⁺-clearance following Ca²⁺ influx was however significantly slowed. Anoxia was also found to inhibit SERCA activity and, to a lesser extent, PMCA activity. Hence, anoxia has multiple influences on Ca²⁺]_i homeostasis in vagal afferent neurons, including depression of ATP-driven Ca²⁺-pumps, modulation of the kinetics of mitochondrial Ca²⁺ buffering/release and Ca²⁺-release from, and depletion of, internal Ca²⁺-stores. These effects are likely to influence sensory neuronal function during ischaemia.