NDLI: Activation and propagation of Ca2+ release from inside the sarcoplasmic reticulum network of mammalian skeletal muscle

Content Provider	PubMed Central
Author	Cully, Tanya R. Edwards, Joshua N. Launikonis, Bradley S.
Copyright Year	2014
Abstract	Skeletal muscle fibres are large and highly elongated cells specialized for producing the force required for posture and movement. The process of controlling the production of force within the muscle, known as excitation–contraction coupling, requires virtually simultaneous release of large amounts of Ca2+ from the sarcoplasmic reticulum (SR) at the level of every sarcomere within the muscle fibre. Here we imaged Ca2+ movements within the SR, tubular (t-) system and in the cytoplasm to observe that the SR of skeletal muscle is a connected network capable of allowing diffusion of Ca2+ within its lumen to promote the propagation of Ca2+ release throughout the fibre under conditions where inhibition of SR ryanodine receptors (RyRs) was reduced. Reduction of cytoplasmic [Mg2+] ([Mg2+]cyto) induced a leak of Ca2+ through RyRs, causing a reduction in SR Ca2+ buffering power argued to be due to a breakdown of SR calsequestrin polymers, leading to a local elevation of [Ca2+]SR. The local rise in [Ca2+]SR, an intra-SR Ca2+ transient, induced a local diffusely rising [Ca2+]cyto. A prolonged Ca2+ wave lasting tens of seconds or more was generated from these events. Ca2+ waves were dependent on the diffusion of Ca2+ within the lumen of the SR and ended as [Ca2+]SR dropped to low levels to inactivate RyRs. Inactivation of RyRs allowed re-accumulation of [Ca2+]SR and the activation of secondary Ca2+ waves in the persistent presence of low [Mg2+]cyto if the threshold [Ca2+]SR for RyR opening could be reached. Secondary Ca2+ waves occurred without an abrupt reduction in SR Ca2+ buffering power. Ca2+ release and wave propagation occurred in the absence of Ca2+-induced Ca2+ release. These observations are consistent with the activation of Ca2+ release through RyRs of lowered cytoplasmic inhibition by [Ca2+]SR or store overload-induced Ca2+ release. Restitution of SR Ca2+ buffering power to its initially high value required imposing normal resting ionic conditions in the cytoplasm, which re-imposed the normal resting inhibition on the RyRs, allowing [Ca2+]SR to return to endogenous levels without activation of store overload-induced Ca2+ release. These results are discussed in the context of how pathophysiological Ca2+ release such as that occurring in malignant hyperthermia can be generated.
Related Links	http://dx.doi.org/10.1113/jphysiol.2014.274274
Ending Page	3746
Page Count	20
Starting Page	3727
File Format	PDF
ISSN	14697793
e-ISSN	14697793
Journal	The Journal of Physiology
Issue Number	Pt 17
Volume Number	592
Language	English
Publisher	Blackwell Science Inc
Publisher Date	2014-09-01
Access Restriction	Open
Rights Holder	Blackwell Science Inc
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Physiology Sports Science

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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