Universität zu Köln

Isensee, Joerg, van Cann, Marianne, Despang, Patrick ORCID: 0000-0002-5258-3653, Araldi, Dioneia ORCID: 0000-0001-8379-2901, Moeller, Katharina, Petersen, Jonas, Schmidtko, Achim, Matthes, Jan ORCID: 0000-0003-2754-1555, Levine, Jon D. and Hucho, Tim ORCID: 0000-0002-4147-9308 (2021). Depolarization induces nociceptor sensitization by Ca(V)1.2-mediated PKA-II activation. J. Cell Biol., 220 (10). NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-8140

Full text not available from this repository.

Abstract

Depolarization drives neuronal plasticity. However, whether depolarization drives sensitization of peripheral nociceptive neurons remains elusive. By high-content screening (HCS) microscopy, we revealed that depolarization of cultured sensory neurons rapidly activates protein kinase A type II (PKA-II) in nociceptors by calcium influx through Ca(V)1.2 channels. This effect was modulated by calpains but insensitive to inhibitors of cAMP formation, including opioids. In turn, PKA-II phosphorylated Ser1928 in the distal C terminus of Ca(V)1.2, thereby increasing channel gating, whereas dephosphorylation of Ser1928 involved the phosphatase calcineurin. Patch-clamp and behavioral experiments confirmed that depolarization leads to calcium-and PKA-dependent sensitization of calcium currents ex vivo and local peripheral hyperalgesia in the skin in vivo. Our data suggest a local activity-driven feed-forward mechanism that selectively translates strong depolarization into further activity and thereby facilitates hypersensitivity of nociceptor terminals by a mechanism inaccessible to opioids.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Isensee, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED van Cann, Marianne UNSPECIFIED UNSPECIFIED UNSPECIFIED Despang, Patrick UNSPECIFIED orcid.org/0000-0002-5258-3653 UNSPECIFIED Araldi, Dioneia UNSPECIFIED orcid.org/0000-0001-8379-2901 UNSPECIFIED Moeller, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Petersen, Jonas UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidtko, Achim UNSPECIFIED UNSPECIFIED UNSPECIFIED Matthes, Jan UNSPECIFIED orcid.org/0000-0003-2754-1555 UNSPECIFIED Levine, Jon D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hucho, Tim UNSPECIFIED orcid.org/0000-0002-4147-9308 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-581623
DOI:	10.1083/jcb.202002083
Journal or Publication Title:	J. Cell Biol.
Volume:	220
Number:	10
Date:	2021
Publisher:	ROCKEFELLER UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1540-8140
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEIN-KINASE-A; CARDIAC CA(V)1.2 CHANNELS; GATED CALCIUM-CHANNELS; CA2+ CHANNEL; ADENYLYL-CYCLASE; CYCLIC-AMP; MICE LACKING; CREB PHOSPHORYLATION; CARBOXYL-TERMINUS; ION CHANNELS Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58162