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Imaging calcium signals in vivo: a powerful tool in physiology and pharmacology.

ABSTRACT: The design and engineering of organic fluorescent Ca(2+) indicators approximately 30 years ago opened the door for imaging cellular Ca(2+) signals with a high degree of temporal and spatial resolution. Over this time, Ca(2+) imaging has revolutionized our approaches for tissue-level spatiotemporal analysis of functional organization and has matured into a powerful tool for in situ imaging of cellular activity in the living animal. In vivo Ca(2+) imaging with temporal resolution at the millisecond range and spatial resolution at micrometer range has been achieved through novel designs of Ca(2+) sensors, development of modern microscopes and powerful imaging techniques such as two-photon microscopy. Imaging Ca(2+) signals in ensembles of cells within tissue in 3D allows for analysis of integrated cellular function, which, in the case of the brain, enables recording activity patterns in local circuits. The recent development of miniaturized compact, fibre-optic-based, mechanically flexible microendoscopes capable of two-photon microscopy opens the door for imaging activity in awake, behaving animals. This development is poised to open a new chapter in physiological experiments and for pharmacological approaches in the development of novel therapies.

SUBMITTER: Russell JT

PROVIDER: S-EPMC3166690 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Imaging calcium signals in vivo: a powerful tool in physiology and pharmacology.

Russell James T JT

British journal of pharmacology 20110801 8

The design and engineering of organic fluorescent Ca(2+) indicators approximately 30 years ago opened the door for imaging cellular Ca(2+) signals with a high degree of temporal and spatial resolution. Over this time, Ca(2+) imaging has revolutionized our approaches for tissue-level spatiotemporal analysis of functional organization and has matured into a powerful tool for in situ imaging of cellular activity in the living animal. In vivo Ca(2+) imaging with temporal resolution at the millisecon ...[more]

PMID: 20718728

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Project description:Voltage-gated calcium channels are required for many key functions in the body. In this review, the different subtypes of voltage-gated calcium channels are described and their physiologic roles and pharmacology are outlined. We describe the current uses of drugs interacting with the different calcium channel subtypes and subunits, as well as specific areas in which there is strong potential for future drug development. Current therapeutic agents include drugs targeting L-type Ca(V)1.2 calcium channels, particularly 1,4-dihydropyridines, which are widely used in the treatment of hypertension. T-type (Ca(V)3) channels are a target of ethosuximide, widely used in absence epilepsy. The auxiliary subunit α2δ-1 is the therapeutic target of the gabapentinoid drugs, which are of value in certain epilepsies and chronic neuropathic pain. The limited use of intrathecal ziconotide, a peptide blocker of N-type (Ca(V)2.2) calcium channels, as a treatment of intractable pain, gives an indication that these channels represent excellent drug targets for various pain conditions. We describe how selectivity for different subtypes of calcium channels (e.g., Ca(V)1.2 and Ca(V)1.3 L-type channels) may be achieved in the future by exploiting differences between channel isoforms in terms of sequence and biophysical properties, variation in splicing in different target tissues, and differences in the properties of the target tissues themselves in terms of membrane potential or firing frequency. Thus, use-dependent blockers of the different isoforms could selectively block calcium channels in particular pathologies, such as nociceptive neurons in pain states or in epileptic brain circuits. Of important future potential are selective Ca(V)1.3 blockers for neuropsychiatric diseases, neuroprotection in Parkinson's disease, and resistant hypertension. In addition, selective or nonselective T-type channel blockers are considered potential therapeutic targets in epilepsy, pain, obesity, sleep, and anxiety. Use-dependent N-type calcium channel blockers are likely to be of therapeutic use in chronic pain conditions. Thus, more selective calcium channel blockers hold promise for therapeutic intervention.

Dataset Information

Imaging calcium signals in vivo: a powerful tool in physiology and pharmacology.

Publications

Imaging calcium signals in vivo: a powerful tool in physiology and pharmacology.

Similar Datasets

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