TRPC3 Channels Are Required for Synaptic Transmission and Motor Coordination

Hartmann, Jana; Dragicevic, Elena; Adelsberger, Helmuth; Henning, Horst A.; Sumser, Martin; Abramowitz, Joel; Blum, Robert; Dietrich, Alexander; Freichel, Marc; Flockerzi, Veit; Birnbaumer, Lutz; Konnerth, Arthur

doi:10.1016/j.neuron.2008.06.009

Cited by 357 publications

(446 citation statements)

References 38 publications

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“…TRPC3 KO (TRPC3 −/− ) and TRPC6 KO (TRPC6 −/− ) mice were previously generated as described (33,34). Each individual KO mouse model was backcrossed for at least five generations into a C57BL/6J background, and their cross yielded the combined TRPC3/TRPC6 dKO (TRPC3/ 6 −/− ) mouse.…”

Section: Methodsmentioning

confidence: 99%

Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy

Seo

Rainer

Hahn

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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167

163

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Significance Cardiac hypertrophy and dysfunction in response to sustained hormonal and mechanical stress are sentinel features of most forms of heart disease. Activation of non–voltage-gated transient receptor potential canonical channels TRPC3 and TRPC6 may contribute to this pathophysiology and provide a therapeutic target. Effects from combined selective inhibition have not been tested previously. Here we report the capability of highly selective TRPC3/6 inhibitors to block pathological hypertrophic signaling in several cell types, including adult cardiac myocytes. We show in vivo redundancy of each channel; individual gene deletion was not protective against sustained pressure overload, whereas combined deletion ameliorated the response. These data strongly support a role for both channels in cardiac disease and the utility of selective combined inhibition.

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Section: Methodsmentioning

confidence: 99%

Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy

Seo

Rainer

Hahn

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

167

163

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“…Kim et al (2003) presented convincing evidence that mGlu 1 can regulate TRPC1 both in heterologous expression systems and in Purkinje cells. However, later studies showed that the Group I mGlu receptor current is reduced by the selective TRPC3 antagonist Pry3 (Ady et al 2014), is absent in TRPC3 KO mice and present in TRPC1 KO mice (Hartmann et al 2008). Together, these data indicate that TRPC3 channels are responsible, at least partially, for the Group I mGlu receptor current at the cerebellar parallel fiber to the Purkinje cell synapse.…”

Section: Trpc Channelsmentioning

confidence: 91%

“…This current can be mimicked by ACPD or DHPG (Hartmann et al 2008), but unlike other Group Imediated responses is resistant or partially resistant to strong intracellular Ca 2+ buffering (BAPTA), inhibition of PLC (U-73122), and inhibition of PKC. Kim et al (2003) presented convincing evidence that mGlu 1 can regulate TRPC1 both in heterologous expression systems and in Purkinje cells.…”

Section: Trpc Channelsmentioning

confidence: 94%

Control of neuronal excitability by Group I metabotropic glutamate receptors

Amb

Jds

et al. 2017

Biophys Rev

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Metabotropic glutamate (mGlu) receptors couple through G proteins to regulate a large number of cell functions. Eight mGlu receptor isoforms have been cloned and classified into three Groups based on sequence, signal transduction mechanisms and pharmacology. This review will focus on Group I mGlu receptors, comprising the isoforms mGlu 1 and mGlu 5 . Activation of these receptors initiates both G protein-dependent and -independent signal transduction pathways. The G-protein-dependent pathway involves mainly Gα q , which can activate PLCβ, leading initially to the formation of IP 3 and diacylglycerol. IP 3 can release Ca 2+ from cellular stores resulting in activation of Ca 2+ -dependent ion channels. Intracellular Ca 2+ , together with diacylglycerol, activates PKC, which has many protein targets, including ion channels. Thus, activation of the G-protein-dependent pathway affects cellular excitability though several different effectors. In parallel, G protein-independent pathways lead to activation of non-selective cationic currents and metabotropic synaptic currents and potentials. Here, we provide a survey of the membrane transport proteins responsible for these electrical effects of Group I metabotropic glutamate receptors.

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“…However, it cannot be excluded that the TRP channel superfamily, just a newcomer in this context, may provide some surprise -and some unexpected answers. The role of these channels in the control of neurite growth and orientation is now established [12,13,85,86], and they play crucial roles in many other aspects of neuronal function, from synaptic transmission [101,102] to sensory transduction [103]; on the other hand, many members are putatively involved in a wide spectrum of pathologies of the nervous system [104,105]. If this will be the case, the development of more specific and selective agonists and antagonists will become the critical issue.…”

Section: Conclusion and Future Developmentsmentioning

confidence: 99%

Calcium Signaling in Neuronal Motility: Pharmacological Tools for Investigating Specific Pathways

Lovisolo

Ariano²,

Distasi³

2012

CMC

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Migration of neurons and neuronal precursors from the site of origin to their final location is a key process in the development of the nervous system and in the correct organization of neuronal structures and circuits. Different modes of migration (mainly radial and tangential) have been described in the last 40 years; for these, as for motility processes involving other cellular types, calcium signalling plays a key role, with influx from the extracellular medium representing the main mechanism, and a more delimited but specific role played by release from intracellular stores.Deciphering the involvement of the different calcium influx pathways has been a major task for cellular neurobiologists, and the availability -or lack -of reliable and selective pharmacological tools has represented the main limiting factor. This review addresses the strategies employed to investigate the role of voltage-dependent calcium channels and of neurotransmitter activated channels, either calcium permeable or not, that directly or indirectly can elicit cytosolic calcium increases; in addition, reference to recent findings on the involvement of other families of calcium permeable channels (such as the transient receptor potential superfamily) is presented. Finally, a brief description of the present -and limited -knowledge of the perturbations of calcium signalling involved in neuronal migration pathologies is provided.

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TRPC3 Channels Are Required for Synaptic Transmission and Motor Coordination

Cited by 357 publications

References 38 publications

Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy

Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy

Control of neuronal excitability by Group I metabotropic glutamate receptors

Calcium Signaling in Neuronal Motility: Pharmacological Tools for Investigating Specific Pathways

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