Linked Life Data

11756491

Source:http://linkedlifedata.com/resource/pubmed/id/11756491

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-12-28
pubmed:abstractText
The physical interaction between the presynaptic vesicle release complex and the large cytoplasmic region linking domains II and III of N-type (Ca(v)2.2) calcium channel alpha(1)B subunits is considered to be of fundamental importance for efficient neurotransmission. By PCR analysis of human brain cDNA libraries and IMR32 cell mRNA, we have isolated novel N-type channel variants, termed Ca(v)2.2-Delta1 and Delta2, which lack large parts of the domain II-III linker region, including the synaptic protein interaction site. They appear to be widely expressed across the human CNS as indicated by RNase protection assays. When expressed in tsA-201 cells, both novel variants formed barium-permeable channels with voltage dependences and kinetics for activation that were similar to those observed with the full-length channel. All three channel types exhibited the hallmarks of prepulse facilitation, which interestingly occurred independently of G-protein betagamma subunits. By contrast, the voltage dependence of steady-state inactivation seen with both Delta1 and Delta2 channels was shifted toward more depolarized potentials, and recovery from inactivation of Delta1 and Delta2 channels occurred more rapidly than that of the full-length channel. Moreover, the Delta1 channel was dramatically less sensitive to both omega-conotoxin MVIIA and GVIA than either the Delta2 variant or the full-length construct. Finally, the domain II-III linker region of neither variant was able to effectively bind syntaxin in vitro. These results suggest that the structure of the II-III linker region is an important determinant of N-type channel function and pharmacology. The lack of syntaxin binding hints at a unique physiological function of these channels.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
82-92
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11756491-Alternative Splicing, pubmed-meshheading:11756491-Barium, pubmed-meshheading:11756491-Binding Sites, pubmed-meshheading:11756491-Brain, pubmed-meshheading:11756491-Calcium Channels, N-Type, pubmed-meshheading:11756491-Cell Line, pubmed-meshheading:11756491-Cloning, Molecular, pubmed-meshheading:11756491-Exons, pubmed-meshheading:11756491-GTP-Binding Proteins, pubmed-meshheading:11756491-Gene Library, pubmed-meshheading:11756491-Humans, pubmed-meshheading:11756491-Introns, pubmed-meshheading:11756491-Kidney, pubmed-meshheading:11756491-Membrane Proteins, pubmed-meshheading:11756491-Molecular Sequence Data, pubmed-meshheading:11756491-Organ Specificity, pubmed-meshheading:11756491-Patch-Clamp Techniques, pubmed-meshheading:11756491-Polymerase Chain Reaction, pubmed-meshheading:11756491-Protein Structure, Tertiary, pubmed-meshheading:11756491-Qa-SNARE Proteins, pubmed-meshheading:11756491-RNA, Messenger, pubmed-meshheading:11756491-Sequence Deletion, pubmed-meshheading:11756491-Sequence Homology, Amino Acid, pubmed-meshheading:11756491-Transcription, Genetic, pubmed-meshheading:11756491-Transfection
pubmed:year
2002
pubmed:articleTitle
Identification and characterization of novel human Ca(v)2.2 (alpha 1B) calcium channel variants lacking the synaptic protein interaction site.
pubmed:affiliation
Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. skaneko@pharm.kyoto-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't