There is both functional and anatomical evidence for the presence of several VGCC subtypes (N, P/Q, L, R) in the cell bodies of aortic baroreceptor afferents, with the N-type being the predominant current. It has been in general inferred that VGCC present at the terminals in approximately similar proportions to the soma and calcium currents of the cell bodies reflect calcium currents at the synapse. However, recent preliminary findings from our laboratory suggest that different population of the VGCCs may play specific roles during different levels and stages of synaptic activation. Using currently available fluorescent imaging techniques, the proposed studies will test the general hypothesis that extended, high frequency baroreceptor activation shifts the primary inward calcium channel flux responsible for exocytosis from the N-type calcium channel to other available calcium channels within the baroreceptor terminal. Further, we will test the hypothesis that different subsets of calcium channels are responsible for baroreceptor exocytosis from the different synaptic vesicle pools found in synaptic terminals. We will use in vitro imaging of synaptic vesicle turnover and intraterminal calcium and imaging of intraterminal calcium in brainstem slices to address are 4 major and distinct aims: 1) To evaluate the contribution of different VGCC subtypes to stimulation evoked vesicle exocytosis at different frequencies. 2) To determine the contribution of different VGCC subtypes to stimulation induced increases in intraterminal calcium. 3) To determine the role of different VGCC in vesicle pool mobilization. 4) To evaluate the effects of sustained hypertension on frequency induced increases in intraterminal calcium and the contribution of the different VGCC subtypes to these changes. Results from these studies are expected to yield novel information that will provide an important advances in our understanding of the cellular mechanisms regulating of baroreceptor neurotransmission. ? ?
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