Dissection of cell-type specific P/Q-type channel function

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Voltage gated Ca2+ channels mediate voltage-dependent Ca2+ influx in subcellular compartments of neurons, triggering such diverse processes as neurotransmitter release, dendritic action potentials and excitation-transcription coupling. Because of their importance for cellular and system function voltage gated Ca2+ channels are therapeutic targets for the treatment of several major diseases including epilepsy, pain, hypertension, stroke and migraine. Several fundamental questions that remain unsolved are how Ca2+ channels are targeted to the appropriate cellular compartments and do cell-type specific functions of the Ca2+ channel exist. In order to understand Ca2+ channel targeting and function in mice, we created and currently characterize mice, where the P/Q-type channel (one of the main voltage gated Ca2+ channels in the brain) can be visualized via a fluorescent tag and can be deleted in a temporal, tissue and cell-type specific manner in the living mice. We will use these mice to dissect the cell/neuron-type specific role of the P/Q-type channels underlying animal behavior and disease processes related to P/Q-type channel expression in the serotonergic system. The research will reveal how synaptic transmission and dendritic Ca2+ signals control action potential firing and serotonin release directly in serotonergic neurons. Thus, we will make a functional connection between serotonin release and P/Q-type channels. This is important because P/Q-type channel mutations cause migraine in humans and migraine patients have low serotonin levels during migraine attacks.