One of the important features of visual information processing in the retina is the conversion of relatively sustained light responses in the outer retina to more diversified responses, including the formation of the transient response, in the inner retina. Increasing evidence suggests that bipolar cells play an active role in retinal processing and that the diversified responses in the inner retina originate, in part, by means of the different forms of transmitter release from bipolar cells. By what mechanism(s) the different forms of transmitter release are generated and to what extent bipolar cell processing contributes to the overall retinal processing remain to be elucidated. The long-term objective of this proposal is to understand the roles of voltage-dependent membrane channels in bipolar cell signal processing. Mammalian retinal bipolar cells express a variety of voltage-dependent channels, including low-voltage-activated (LVA) and high-voltage-activated (HVA) Ca2+ channels at the axon terminals and voltage-gated Na+ channels in a subset of cone bipolar cells. The physiological roles of multiple voltage-activated Ca2+ channels and voltage-gated Na+ channels in bipolar cell signal processing will be investigated. The first part of this proposal is to study the roles of LVA and L-type HVA Ca2+ channels in bipolar cell transmitter release.
Specific aim 1 will determine the Ca2+ channel type(s) located at the axon terminals and involved in transmitter release of different subtypes of bipolar cells.
Specific aim 2 will determine the temporal properties of transmitter release from bipolar cells during the activation of LVA and L-type Ca2+ channels. The second part of this application is to study the roles of voltage-dependent membrane channels in shaping bipolar cell response waveforms.
Specific aim 3 will determine the roles of different voltage-dependent channels in the spontaneous and evoked response waveforms in isolated bipolar cells.
Specific aim 4 will determine the subtypes of bipolar cells expressing Na+ channels and the contribution of Na+ currents in bipolar cell light response waveforms. The studies will be carried out with isolated bipolar cells and with bipolar cells in retinal slice preparations of mammalian retinas. Patch-clamp recording and optical Ca2+ imaging methods will be employed. The knowledge we gain from these studies will lead to a better understanding of basic visual information processing in the mammalian retina. The understanding of the role of voltage-activated Ca2+ channels in synaptic transmission may also provide insight for identifying the mechanism of diseases caused by synaptic dysfunction.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012180-07
Application #
6524945
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Hunter, Chyren
Project Start
1997-09-30
Project End
2006-09-29
Budget Start
2002-09-30
Budget End
2003-09-29
Support Year
7
Fiscal Year
2002
Total Cost
$295,801
Indirect Cost
Name
Wayne State University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
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
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
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
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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