scholarly journals Deficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hieu Hoang Trung ◽  
Toru Yoshihara ◽  
Akito Nakao ◽  
Katsumi Hayashida ◽  
Yoshiki Hirata ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Fear Conditioning ◽  
Open Field ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Regulatory Subunit ◽  
Type I ◽  
Schaffer Collateral ◽  
Normal Behavior ◽  
Collateral Pathway

AbstractThe RIβ subunit of cAMP-dependent protein kinase (PKA), encoded by Prkar1b, is a neuronal isoform of the type I regulatory subunit of PKA. Mice lacking the RIβ subunit exhibit normal long-term potentiation (LTP) in the Schaffer collateral pathway of the hippocampus and normal behavior in the open-field and fear conditioning tests. Here, we combined genetic, electrophysiological, and behavioral approaches to demonstrate that the RIβ subunit was involved in body tremor, LTP in the Schaffer collateral pathway, and fear conditioning memory in rats. Genetic analysis of WTC-furue, a mutant strain with spontaneous tremors, revealed a deletion in the Prkar1b gene of the WTC-furue genome. Prkar1b-deficient rats created by the CRISPR/Cas9 system exhibited body tremor. Hippocampal slices from mutant rats showed deficient LTP in the Schaffer collateral–CA1 synapse. Mutant rats also exhibited decreased freezing time following contextual and cued fear conditioning, as well as increased exploratory behavior in the open field. These findings indicate the roles of the RIβ subunit in tremor pathogenesis and contextual and cued fear memory, and suggest that the hippocampal and amygdala roles of this subunit differ between mice and rats and that rats are therefore beneficial for exploring RIβ function.

Transient Removal of Extracellular Mg2+ Elicits Persistent Suppression of LTP at Hippocampal CA1 Synapses Via PKC Activation

2000 ◽  
Vol 84 (3) ◽  
pp. 1279-1288 ◽  
Author(s):  
Kuei-Sen Hsu ◽  
Wen-Chia Ho ◽  
Chiung-Chun Huang ◽  
Jing-Jane Tsai
Keyword(s):  
Nmda Receptor ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Suppressive Effect ◽  
Dependent Protein Kinase ◽  
Dependent Protein

Previous work has shown that seizure-like activity can disrupt the induction of long-term potentiation (LTP). However, how seizure-like event disrupts the LTP induction remains unknown. To understand the cellular and molecular mechanisms underlying this process better, a set of studies was implemented in area CA1 of rat hippocampal slices using extracellular recording methods. We showed here that prior transient seizure-like activity generated by perfused slices with Mg2+-free artificial cerebrospinal fluid (ACSF) exhibited a persistent suppression of LTP induction. This effect lasted between 2 and 3 h after normal ACSF replacement and was specifically inhibited by N-methyl-d-aspartate (NMDA) receptor antagonistd-2-amino-5-phosphovaleric acid (d-APV) and L-type voltage-operated Ca2+ channel (VOCC) blocker nimodipine, but not by non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In addition, this suppressive effect was specifically blocked by the selective protein kinase C (PKC) inhibitor NPC-15437. However, neither Ca2+/calmodulin-dependent protein kinase II inhibitor KN-62 nor cAMP-dependent protein kinase inhibitor Rp-adenosine 3′,5′-cyclic monophosphothioate (Rp-cAMPS) affected this suppressive effect. This persistent suppression of LTP was not secondary to the long-lasting changes in NMDA receptor activation, because the isolated NMDA receptor–mediated responses did not show a long-term enhancement in response to a 30-min Mg2+-free ACSF application. Additionally, in prior Mg2+-free ACSF–treated slices, the entire frequency-response curve of LTP and long-term depression (LTD) is shifted systematically to favor LTD. These results suggest that the increase of Ca2+ influx through NMDA channels and L-type VOCCs in turn triggering a PKC-dependent signaling cascade is a possible cellular basis underlying this seizure-like activity-induced inhibition of LTP.

Regulation of lung epithelial cell morphology by cAMP-dependent protein kinase type I isozyme

2001 ◽  
Vol 280 (6) ◽  
pp. L1282-L1289 ◽  
Author(s):  
Stephanie E. Porter ◽  
Lori D. Dwyer-Nield ◽  
Alvin M. Malkinson
Keyword(s):  
Protein Kinase ◽  
Cell Junctions ◽  
Actin Binding ◽  
Regulatory Subunit ◽  
Type I ◽  
Stable Transfection ◽  
Dependent Protein Kinase ◽  
Camp Dependent Protein Kinase ◽  
Lung Epithelial ◽  
Dependent Protein

Cell shape is mediated in part by the actin cytoskeleton and the actin-binding protein vinculin. These proteins in turn are regulated by protein phosphorylation. We assessed the contribution of cAMP-dependent protein kinase A isozyme I (PKA I) to lung epithelial morphology using the E10/E9 sibling cell lines. PKA I concentration is high in flattened, nontumorigenic E10 cells but low in their round E9 transformants. PKA I activity was lowered in E10 cells by stable transfection with a dominant negative RIα mutant of the PKA I regulatory subunit and was raised in E9 cells by stable transfection with a wild-type Cα catalytic subunit construct. Reciprocal changes in morphology ensued. E10 cells became rounder and grew in colonies, their actin microfilaments were disrupted, and vinculin localization at cell-cell junctions was diminished. The converse occurred in E9 cells on elevating their PKA I content. Demonstration that PKA I is responsible for the dichotomy in these cellular behaviors suggests that manipulating PKA I concentrations in lung cancer would provide useful adjuvant therapy.

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