Voltage-gated Cav channels mediate activity-dependent Ca2+ signals required for gene transcription and neurotransmission. Ca2+-dependent inactivation and facilitation (CDI and CDF, respectively) allow Cav channels to adjust Ca2+ influx according to neuronal activity, thereby fine-tuning Ca2+ signals that control neuronal excitability and synaptic plasticity. The rationale for the proposed research is that defining how Cav channels generate and maintain Ca2+ signals will answer longstanding questions regarding the heterogeneous properties of Cav channels in neurons and enable new mechanistic inquiries into the roles of specific Cav channels in orchestrating the normal development and function of the nervous system. The expected outcomes of the proposed research are: establishment of a new role for calretinin as a dynamic regulator of effectors including Cav2.
1 (Aim 1); and elucidation of a mechanism responsible for the """"""""long-lasting"""""""" properties and functional impact of neuronal Cav1 L-type currents (Aim 2). We believe that the proposed research will make a lasting and positive impact: the Cav channel regulatory mechanisms it will define will likely facilitate the development of novel therapeutics for neurological and neuropsychiatric disorders resulting from dysregulation of neuronal Ca2+ signals.

Public Health Relevance

The proposed research will characterize the mechanisms and physiological significance of factors that modulate voltage-gated Ca2+ channels neurons. We will elucidate new cellular and molecular mechanisms, which may be altered in neurological and neuropsychiatric diseases.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Silberberg, Shai D
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University of Iowa
Schools of Medicine
Iowa City
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Haeseleer, Françoise; Williams, Brittany; Lee, Amy (2016) Characterization of C-terminal Splice Variants of Cav1.4 Ca2+ Channels in Human Retina. J Biol Chem 291:15663-73
Thomas, Jessica R; Lee, Amy (2016) Measuring Ca2+-Dependent Modulation of Voltage-Gated Ca2+ Channels in HEK-293T Cells. Cold Spring Harb Protoc 2016:pdb.prot087213
Hardie, Jason; Lee, Amy (2016) Decalmodulation of Cav1 channels by CaBPs. Channels (Austin) 10:33-7
Krueger, Jamie N; Moore, Shannon J; Parent, Rachel et al. (2016) A novel mouse model of the aged brain: Over-expression of the L-type voltage-gated calcium channel CaV1.3. Behav Brain Res :
Stanika, Ruslan; Campiglio, Marta; Pinggera, Alexandra et al. (2016) Splice variants of the CaV1.3 L-type calcium channel regulate dendritic spine morphology. Sci Rep 6:34528
Yang, Tian; Scholl, Elizabeth S; Pan, Ning et al. (2016) Expression and Localization of CaBP Ca2+ Binding Proteins in the Mouse Cochlea. PLoS One 11:e0147495
Lee, Amy; Wang, Shiyi; Williams, Brittany et al. (2015) Characterization of Cav1.4 complexes (α11.4, β2, and α2δ4) in HEK293T cells and in the retina. J Biol Chem 290:1505-21
Scharinger, Anja; Eckrich, Stephanie; Vandael, David H et al. (2015) Cell-type-specific tuning of Cav1.3 Ca(2+)-channels by a C-terminal automodulatory domain. Front Cell Neurosci 9:309
Joiner, Mei-Ling A; Lee, Amy (2015) Voltage-Gated Cav1 Channels in Disorders of Vision and Hearing. Curr Mol Pharmacol 8:143-8
Cao, Yan; Sarria, Ignacio; Fehlhaber, Katherine E et al. (2015) Mechanism for Selective Synaptic Wiring of Rod Photoreceptors into the Retinal Circuitry and Its Role in Vision. Neuron 87:1248-60

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