Study of Presynaptic Calcium Channels and a Novel Calcium Channel Calhm1




Ozkan, Emin D.

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Calcium signaling is essential for all cellular processes. In brain these processes include basic synaptic transmission, modification of established synapses, elimination of synapses as well as elimination of whole neurons by way of apoptosis. In this thesis, we have studied two of these processes. One process is synaptic targeting of presynaptic calcium channels. We have tested the hypothesis that synaptic targeting of presynaptic calcium channels depends on carboxy terminal interactions with mint and CASK proteins. To this end we have used mice mutant for P/Q-type calcium channel. Our experiments show that a P/Q-type calcium channel without its carboxy terminal can partially contribute to synaptic transmission. Secondly we have studied the role of Calhm1 gene in modulating calcium signaling pathways. For this purpose we have used overexpression of Calhm1 gene in HEK293 cells as well as in dissociated neuronal cultures. Our experiments show that Calhm1 modulates calcium signaling in HEK293 cell and in certain neurons. Calhm1 overexpression also modulates spontaneous synaptic transmission.

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