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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS084190-01A1
Application #
8682329
Study Section
Special Emphasis Panel (ZRG1-MDCN-C (04))
Program Officer
Silberberg, Shai D
Project Start
2013-12-15
Project End
2018-11-30
Budget Start
2013-12-15
Budget End
2014-11-30
Support Year
1
Fiscal Year
2014
Total Cost
$411,783
Indirect Cost
$133,885
Name
University of Iowa
Department
Physiology
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
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Kim, K Y; Scholl, E S; Liu, X et al. (2014) Localization and expression of CaBP1/caldendrin in the mouse brain. Neuroscience 268:33-47
Inagaki, Akira; Frank, C Andrew; Usachev, Yuriy M et al. (2014) Pharmacological correction of gating defects in the voltage-gated Ca(v)2.1 Ca²? channel due to a familial hemiplegic migraine mutation. Neuron 81:91-102