The auxiliary subunit gamma 1 of the skeletal muscle L-type Ca2+ channel is an endogenous Ca2+ antagonist.

The auxiliary subunit gamma 1 of the skeletal muscle L-type Ca2+ channel is an endogenous Ca2+ antagonist. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

The auxiliary subunit gamma 1 of the skeletal muscle L-type Ca2+ channel is an endogenous Ca2+ antagonist. Abstract Text:

Zoita Andronache,Daniel Ursu,Simone Lehnert,Marc Freichel,Veit Flockerzi,Werner Melzer,Zoita Andronache,Daniel Ursu,Simone Lehnert,Marc Freichel,Veit Flockerzi,Werner Melzer,

Ca2+ channels play crucial roles in cellular signal transduction and are important targets of pharmacological agents. They are also associated with auxiliary subunits exhibiting functions that are still incompletely resolved. Skeletal muscle L-type Ca2+ channels (dihydropyridine receptors, DHPRs) are specialized for the remote voltage control of type 1 ryanodine receptors (RyR1) to release stored Ca2+. The skeletal muscle-specific gamma subunit of the DHPR (gamma 1) down-modulates availability by altering its steady state voltage dependence. The effect resembles the action of certain Ca2+ antagonistic drugs that are thought to stabilize inactivated states of the DHPR. In the present study we investigated the cross influence of gamma 1 and Ca2+ antagonists by using wild-type (gamma+/+) and gamma 1 knockout (gamma-/-) mice. We studied voltage-dependent gating of both L-type Ca2+ current and Ca2+ release and the allosteric modulation of drug binding. We found that 10 microM diltiazem, a benzothiazepine drug, more than compensated for the reduction in high-affinity binding of the dihydropyridine agent isradipine caused by gamma 1 elimination; 5 muM devapamil [(-)D888], a phenylalkylamine Ca2+ antagonist, approximately reversed the right-shifted voltage dependence of availability and the accelerated recovery kinetics of Ca2+ current and Ca2+ release. Moreover, the presence of gamma 1 altered the effect of D888 on availability and strongly enhanced its impact on recovery kinetics demonstrating that gamma 1 and the drug do not act independently of each other. We propose that the gamma 1 subunit of the DHPR functions as an endogenous Ca2+ antagonist whose task may be to minimize Ca2+ entry and Ca2+ release under stress-induced conditions favoring plasmalemma depolarization.

The auxiliary subunit gamma 1 of the skeletal muscle L-type Ca2+ channel is an endogenous Ca2+ antagonist. Publishing Authors By Initials

Z Andronache,D Ursu,S Lehnert,M Freichel,V Flockerzi,W Melzer,Z Andronache,D Ursu,S Lehnert,M Freichel,V Flockerzi,W Melzer,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

The auxiliary subunit gamma 1 of the skeletal muscle L-type Ca2+ channel is an endogenous Ca2+ antagonist. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 17885-90

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 31

MONTH: 10

YEAR: 2007

The auxiliary subunit gamma 1 of the skeletal muscle L-type Ca2+ channel is an endogenous Ca2+ antagonist. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

The auxiliary subunit gamma 1 of the skeletal muscle L-type Ca2+ channel is an endogenous Ca2+ antagonist. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: The auxiliary subunit gamma 1 of the skeletal muscle L-type Ca2+ channel is an endogenous Ca2+ antagonist. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for The auxiliary subunit gamma 1 of the skeletal muscle L-type Ca2+ channel is an endogenous Ca2+ antagonist.

AFFILIATION: Institut für Angewandte Physiologie, Universität Ulm, Albert-Einstein-Allee 11, D-89069 Ulm, Germany.

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Proc Natl Acad Sci U S A

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

The auxiliary subunit gamma 1 of the skeletal muscle L-type Ca2+ channel is an endogenous Ca2+ antagonist Related Publications

• A common variant of the interleukin 6 receptor (IL-6r) gene increases IL-6r and IL-6 levels, without other inflammatory effects.
• An interleukin-18 polymorphism is associated with reduced serum concentrations and better physical functioning in older people.
• Child and adolescent telepsychiatry: utilization and satisfaction.
• Community-acquired Klebsiella pneumoniae meningitis in an alcoholic patient with an infected pancreatic pseudocyst; a case report and review of literature.
• Diagnosis of duodenal leaks from kidney-pancreas transplants in patients with duodenovesical anastomoses: value of CT cystography.
• Epidemiology of balance and dizziness in a national population: findings from the English Longitudinal Study of Ageing.
• Examinations of the pathology of the rotator cuff.
• Feasibility, acceptability, and sustainability of telepsychiatry for children and adolescents.
• Flowering of strict photoperiodic Nicotiana varieties in non-inductive conditions by transgenic approaches.
• Genetic polymorphisms and human aging: association studies deliver.
• Hospital-based study of viridans streptococcal bacteraemia in children and adults.
• Image-guided robotics and navigation.
• Neighborhood deprivation, individual socioeconomic status, and cognitive function in older people: analyses from the English Longitudinal Study of Ageing.
• Newborn care by pediatric hospitalists in a community hospital: effect on physician productivity and financial performance.
• Obliquely propagating dust-density waves.
• Origin and evolution of arthropod visual systems.
• Physical activity in middle-aged adults reduces risks of functional impairment independent of its effect on weight.
• Smoking cessation and transition into retirement: analyses from the English Longitudinal Study of Ageing.
• Telepsychiatry with incarcerated youth.
• The auxiliary subunit gamma 1 of the skeletal muscle L-type Ca2+ channel is an endogenous Ca2+ antagonist.
• The prevalence of chlamydiae of bulls from six bull studs in Germany.
• What level of alcohol consumption is hazardous for older people? Functioning and mortality in U.S. and English national cohorts.
• [Artificial human donor insemination as a treatment possibility for sterile couples at the gynecologic clinic of the Chemnitz "Friedrich Wolf" district hospital]
• [Management of functional sterility using clomiphene and cyclophenyl at the Karl-Marx-Stadt District Hospital Gynecologic Clinic]
• [Management of functional sterility using clomiphene. A clinical experience report]
• [Maritogenic insemination - a contribution to the treatment of childless couples. Report on clinical experiences]
• [Mid-foot pain after vacation in Spain]
• [Precanceroses of the cervix uteri--contribution to diagnosis within the scope of pregnancy interruption]
• [Study of voluntary psychomotor initiative in mental and neurological diseases.]
• [Therapeutic results in hyperprolactinemic sterility patients]