The regulation of transmitter release at retinal bipolar cell terminals is important for visual signal processing from the outer retina to the inner retina in vertebrates. Although the central role of Ca2+ in transmitter release at presynaptic terminals is well established, the dynamic regulation of intracellular Ca2+ concentrations ([Ca2+]i) at presynaptic terminals and its effect on transmitter release is still largely unclear. The objective of this proposal is to study the roles of Ca2+ channels and GABA receptors in the regulation of Ca2+ dynamics at the axon terminal of mammalian bipolar cells. Experiments will be performed in solitary rat and mouse bipolar cells. Ca2+-sensitive fluorescence dyes will be used. Fluorescence signals will be monitored by a high resolution confocal microscope based imaging system. Cell's membrane potential will be controlled by patch-clamp methods and, alternatively, cell depolarization will be evoked by high K+.
The specific aims are: I) to determine the spatial distribution of different types of Ca2+ channels in bipolar cells; 2) to characterize the Ca2+ transients at bipolar cell terminals during the activation of different Ca2+ channels and during cell depolarization that mimics bipolar light response waveforms; 3) to characterize the distinct effects of GABA A and GABA C receptors on the regulation of the Ca2+ transients at bipolar cell terminals; 4) to determine the spatial distribution of GABA receptors and the possible co-localization of specific types of GABA receptors with specific type(s) of Ca2+ channels. The knowledge we gain from these studies will not only lead to a better understanding of basic visual signal processing in mammalian retina but will also contribute to our knowledge of the roles of Ca2+ and inhibitory neurotransmitters in synaptic transmission in the CNS.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Visual Sciences C Study Section (VISC)
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Hunter, Chyren
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Wayne State University
Anatomy/Cell Biology
Schools of Medicine
United States
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Hu, Caiping; Bi, Anding; Pan, Zhuo-Hua (2009) Differential expression of three T-type calcium channels in retinal bipolar cells in rats. Vis Neurosci 26:177-87
Cui, Jinjuan; Pan, Zhuo-Hua (2008) Two types of cone bipolar cells express voltage-gated Na+ channels in the rat retina. Vis Neurosci 25:635-45
Bi, Anding; Cui, Jinjuan; Ma, Yu-Ping et al. (2006) Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration. Neuron 50:23-33
Ma, Yu-Ping; Cui, Jinjuan; Pan, Zhuo-Hua (2005) Heterogeneous expression of voltage-dependent Na+ and K+ channels in mammalian retinal bipolar cells. Vis Neurosci 22:119-33
Cui, Jinjuan; Ma, Yu-Ping; Lipton, Stuart A et al. (2003) Glycine receptors and glycinergic synaptic input at the axon terminals of mammalian retinal rod bipolar cells. J Physiol 553:895-909
Ma, Yu-Ping; Cui, Jinjuan; Hu, Hui-Juan et al. (2003) Mammalian retinal bipolar cells express inwardly rectifying K+ currents (IKir) with a different distribution than that of Ih. J Neurophysiol 90:3479-89
Ma, Yu-Ping; Pan, Zhuo-Hua (2003) Spontaneous regenerative activity in mammalian retinal bipolar cells: roles of multiple subtypes of voltage-dependent Ca2+ channels. Vis Neurosci 20:131-9
Hu, Hui-Juan; Pan, Zhuo-Hua (2002) Differential expression of K+ currents in mammalian retinal bipolar cells. Vis Neurosci 19:163-73
Pan, Z H; Hu, H J; Perring, P et al. (2001) T-type Ca(2+) channels mediate neurotransmitter release in retinal bipolar cells. Neuron 32:89-98
Pan, Z H (2001) Voltage-activated Ca2+ channels and ionotropic GABA receptors localized at axon terminals of mammalian retinal bipolar cells. Vis Neurosci 18:279-88

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