Linked Life Data

11997265

Source:http://linkedlifedata.com/resource/pubmed/id/11997265

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2002-5-8
pubmed:abstractText
The actin-binding proteins dystrophin and alpha-actinin are members of a family of actin-binding proteins that may link the cytoskeleton to membrane proteins such as ion channels. Previous work demonstrated that the activity of Ca2+ channels can be regulated by agents that disrupt or stabilize the cytoskeleton. In the present study, we employed immunohistochemical and electrophysiological techniques to investigate the potential regulation of cardiac L-type Ca2+ channel activity by dystrophin and alpha-actinin in cardiac myocytes and in heterologous cells. Both actin-binding proteins were found to colocalize with the Ca2+ channel in mouse cardiac myocytes and to modulate channel function. Inactivation of the Ca2+ channel in cardiac myocytes from mice lacking dystrophin (mdx mice) was reduced compared with that in wild-type myocytes, voltage dependence of activation was shifted by 5 mV to more positive potentials, and stimulation by the beta-adrenergic pathway and the dihydropyridine agonist BAY K 8644 was increased. Furthermore, heterologous coexpression of the Ca2+ channel with muscle, but not nonmuscle, forms of alpha-actinin was also found to reduce inactivation. As might be predicted from a reduction of Ca2+ channel inactivation, a prolonging of the mouse electrocardiogram QT was observed in mdx mice. These results suggest a combined role for dystrophin and alpha-actinin in regulating the activity of the cardiac L-type Ca2+ channel and a potential mechanism for cardiac dysfunction in Duchenne and Becker muscular dystrophies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0363-6143
pubmed:author
pubmed:issnType
Print
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C1502-11
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11997265-3-Pyridinecarboxylic acid..., pubmed-meshheading:11997265-Actinin, pubmed-meshheading:11997265-Adrenergic beta-Agonists, pubmed-meshheading:11997265-Animals, pubmed-meshheading:11997265-Calcium Channel Agonists, pubmed-meshheading:11997265-Calcium Channels, L-Type, pubmed-meshheading:11997265-Cell Line, pubmed-meshheading:11997265-Cells, Cultured, pubmed-meshheading:11997265-Disease Models, Animal, pubmed-meshheading:11997265-Dystrophin, pubmed-meshheading:11997265-Electrocardiography, pubmed-meshheading:11997265-Fluorescent Antibody Technique, pubmed-meshheading:11997265-Heart, pubmed-meshheading:11997265-Heart Rate, pubmed-meshheading:11997265-Humans, pubmed-meshheading:11997265-Membrane Potentials, pubmed-meshheading:11997265-Mice, pubmed-meshheading:11997265-Mice, Inbred C57BL, pubmed-meshheading:11997265-Mice, Inbred mdx, pubmed-meshheading:11997265-Muscular Dystrophy, Animal, pubmed-meshheading:11997265-Myocardium, pubmed-meshheading:11997265-Patch-Clamp Techniques, pubmed-meshheading:11997265-Protein Isoforms, pubmed-meshheading:11997265-Rabbits, pubmed-meshheading:11997265-Rats
pubmed:year
2002
pubmed:articleTitle
Regulation of the cardiac L-type Ca2+ channel by the actin-binding proteins alpha-actinin and dystrophin.
pubmed:affiliation
Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't