Journal
CELL AND TISSUE RESEARCH
Volume 357, Issue 2, Pages 463-476Publisher
SPRINGER
DOI: 10.1007/s00441-014-1936-3
Keywords
Voltage-gated calcium channels; L-type calcium channels; Brain; Memory; Neurodegeneration; Drug addiction; Schizophrenia; Mouse; Human
Categories
Ask authors/readers for more resources
The use of specific activators and inhibitors that penetrate the central nervous system has suggested an essential functional role of L-type calcium channels (LTCC) in several important physiological processes of the brain, including the modulation of the mesoaccumbal dopamine signalling pathway, synaptic transmission of auditory stimuli and synaptic plasticity of neutral and aversive learning and memory processes. However, the lack of selectivity of available pharmacological agents towards the most prominent LTCC isoforms in the brain, namely Ca(v)1.2 and Ca(v)1.3, has hampered the elucidation of the precise contribution made by each specific channel isoform within these specific physiological processes. Modern genetic approaches, both in rodents and in human, have recently enhanced our understanding of the selective functional roles of Ca(v)1.2 and Ca(v)1.3 channels. In rodents, the characterisation of global and conditional isoform-specific knockouts suggests a contribution of Ca(v)1.2 channels in spatial memory formation, whereas Ca(v)1.3 channels seem to be involved in the consolidation of fear memories and in neurodegenerative mechanisms associated with the development of Parkinson's disease. With regard to the molecular mechanisms underlying drug addiction, Ca(v)1.3 channels are necessary for the development and Ca(v)1.2 channels for the expression of cocaine and amphetamine behavioural sensitisation. In humans, both the identification of naturally occurring LTCC variants (channelopathies) and unbiased genome-wide association studies have linked LTCCs to working memory performance in healthy individuals and schizophrenic patients. Individually, CACNA1C polymorphisms and CACNA1D variants have been linked to a variety of psychiatric diseases and to congenital deafness, respectively. However, the contribution of individual LTCCs and their polymorphisms to human brain function and diseases remains unclear, necessitating the use of isoform-specific pharmacological agents.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available