In:
The Journal of Physiology, Wiley, Vol. 595, No. 14 ( 2017-07-15), p. 4769-4784
Abstract:
The role of trimeric intracellular cation (TRIC) channels is not known, although evidence suggests they may regulate ryanodine receptors (RyR) via multiple mechanisms. We therefore investigated whether Tric‐a gene knockout (KO) alters the single‐channel function of skeletal RyR (RyR1). We find that RyR1 from Tric‐a KO mice are more sensitive to inhibition by divalent cations, although they respond normally to cytosolic Ca 2+ , ATP, caffeine and luminal Ca 2+ . In the presence of Mg 2+ , ATP cannot effectively activate RyR1 from Tric‐a KO mice. Additionally, RyR1 from Tric‐a KO mice are not activated by protein kinase A phosphorylation, demonstrating a defect in the ability of β‐adrenergic stimulation to regulate sarcoplasmic reticulum (SR) Ca 2+ ‐release. The defective RyR1 gating that we describe probably contributes significantly to the impaired SR Ca 2+ ‐release observed in skeletal muscle from Tric‐a KO mice, further highlighting the importance of TRIC‐A for normal physiological regulation of SR Ca 2+ ‐release in skeletal muscle.
Type of Medium:
Online Resource
ISSN:
0022-3751
,
1469-7793
DOI:
10.1113/tjp.2017.595.issue-14
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
1475290-6
SSG:
12
Permalink