Inhibition of dendritic Ca2+ spikes by GABAB receptors in cortical pyramidal neurons is mediated by a direct Gi/o- -subunit interaction with Cav1 channels

Pérez Garci, Enrique; Larkum, Matthew; Nevian, Thomas (2013). Inhibition of dendritic Ca2+ spikes by GABAB receptors in cortical pyramidal neurons is mediated by a direct Gi/o- -subunit interaction with Cav1 channels. Journal of physiology, 591(7), pp. 1599-1612. Wiley-Blackwell 10.1113/jphysiol.2012.245464

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Voltage-dependent calcium channels (VDCCs) serve a wide range of physiological functions and their activity is modulated by different neurotransmitter systems. GABAergic inhibition of VDCCs in neurons has an important impact in controlling transmitter release, neuronal plasticity, gene expression and neuronal excitability. We investigated the molecular signalling mechanisms by which GABAB receptors inhibit calcium-mediated electrogenesis (Ca2+ spikes) in the distal apical dendrite of cortical layer 5 pyramidal neurons. Ca2+ spikes are the basis of coincidence detection and signal amplification of distal tuft synaptic inputs characteristic for the computational function of cortical pyramidal neurons. By combining dendritic whole-cell recordings with two-photon fluorescence Ca2+ imaging we found that all subtypes of VDCCs were present in the Ca2+ spike initiation zone, but that they contribute differently to the initiation and sustaining of dendritic Ca2+ spikes. Particularly, Cav1 VDCCs are the most abundant VDCC present in this dendritic compartment and they generated the sustained plateau potential characteristic for the Ca2+ spike. Activation of GABAB receptors specifically inhibited Cav1 channels. This inhibition of L-type Ca2+ currents was transiently relieved by strong depolarization but did not depend on protein kinase activity. Therefore, our findings suggest a novel membrane-delimited interaction of the Gi/o-βγ-subunit with Cav1 channels identifying this mechanism as the general pathway of GABAB receptor-mediated inhibition of VDCCs. Furthermore, the characterization of the contribution of the different VDCCs to the generation of the Ca2+ spike provides new insights into the molecular mechanism of dendritic computation.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology
10 Strategic Research Centers > Center for Cognition, Learning and Memory (CCLM)

UniBE Contributor:

Pérez Garci, Enrique; Larkum, Matthew and Nevian, Thomas

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0022-3751

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Stefan von Känel-Zimmermann

Date Deposited:

12 Jun 2014 08:37

Last Modified:

13 Jan 2016 16:23

Publisher DOI:

10.1113/jphysiol.2012.245464

PubMed ID:

23184512

BORIS DOI:

10.7892/boris.47780

URI:

https://boris.unibe.ch/id/eprint/47780

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