NCS-1 Protein upregulation Facilitates Chronic Hypoxia-induced Respiratory Adaptation in Lymnaea stagnalis

Chronic hypoxia is a consequence of many common diseases, including sleep apnea and chronic lung disease. As there is no cure for many of these diseases, managing the symptoms of these diseases, including hypoxia is of great clinical importance. Preliminary data from the Feng lab show that the calcium binding protein neuronal calcium sensor-1 (NCS-1) is upregulated in the central nervous system of the freshwater pond snail Lymnaea stagnalis following chronic hypoxia treatment. This upregulation coincides with increased aerial respiratory activity. Furthermore, knockdown of NCS-1 attenuates hypoxia-induced facilitation of aerial respiration. Since this aerial respiratory activity is controlled by a respiratory central pattern generator (rCPG), it is hypothesized that hypoxia-induced upregulation of NCS-1 may regulate rCPG activity. Using intercellular sharp electrode recording, I show that in response to chronic hypoxia treatment, there is increased bursting activity and altered action potential profile in the pacemaker neuron of the rCPG, RPeD1. Knockdown of NCS-1 partially prevents these hypoxia-induced changes. Our findings suggest that NCS-1 upregulation is necessary for chronic hypoxia-induced respiratory adaptation.MAS