Linked Life Data

10884302

Source:http://linkedlifedata.com/resource/pubmed/id/10884302

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2000-8-3
pubmed:abstractText
Electrophysiological and molecular studies have revealed considerable heterogeneity in voltage-gated K(+) currents and in the subunits that underlie these channels in mammalian neurons. At present, however, the relationship between native K(+) currents and cloned subunits is poorly understood. In the experiments here, a molecular genetic approach was exploited to define the molecular correlate of the fast transient outward K(+) current, I(Af), in sympathetic neurons and to explore the functional role of I(Af) in shaping action potential waveforms and controlling repetitive firing patterns. Using the biolistic gene gun, cDNAs encoding a dominant negative mutant Kv4.2 alpha-subunit (Kv4.2W362F) and enhanced green fluorescent protein (EGFP) were introduced into rat sympathetic neurons in vitro. Whole-cell voltage-clamp recordings obtained from EGFP-positive cells revealed that I(Af) is selectively eliminated in cells expressing Kv4.2W362F, demonstrating that Kv4 alpha-subunits underlie I(Af) in sympathetic neurons. In addition, I(Af) density is increased significantly in cells overexpressing wild-type Kv4.2. In cells expressing Kv4.2W362F, input resistances are increased and (current) thresholds for action potential generation are decreased, demonstrating that I(Af) plays a pivotal role in regulating excitability. Expression of Kv4.2W362F and elimination of I(Af) also alters the distribution of repetitive firing patterns observed in response to a prolonged injection of depolarizing current. The wild-type superior cervical ganglion is composed of phasic, adapting, and tonic firing neurons. Elimination of I(Af) increases the percentage of adapting cells by shifting phasic cells to the adapting firing pattern, and increased I(Af) density reduces the number of adapting cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0270-6474
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5191-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10884302-Action Potentials, pubmed-meshheading:10884302-Adaptation, Physiological, pubmed-meshheading:10884302-Animals, pubmed-meshheading:10884302-Biolistics, pubmed-meshheading:10884302-Cell Count, pubmed-meshheading:10884302-Cells, Cultured, pubmed-meshheading:10884302-Coculture Techniques, pubmed-meshheading:10884302-Green Fluorescent Proteins, pubmed-meshheading:10884302-Ion Transport, pubmed-meshheading:10884302-Luminescent Proteins, pubmed-meshheading:10884302-Mutagenesis, Site-Directed, pubmed-meshheading:10884302-Neuroglia, pubmed-meshheading:10884302-Neurons, pubmed-meshheading:10884302-Patch-Clamp Techniques, pubmed-meshheading:10884302-Potassium, pubmed-meshheading:10884302-Potassium Channels, pubmed-meshheading:10884302-Potassium Channels, Voltage-Gated, pubmed-meshheading:10884302-Rats, pubmed-meshheading:10884302-Rats, Long-Evans, pubmed-meshheading:10884302-Recombinant Proteins, pubmed-meshheading:10884302-Shal Potassium Channels, pubmed-meshheading:10884302-Superior Cervical Ganglion
pubmed:year
2000
pubmed:articleTitle
Elimination of the fast transient in superior cervical ganglion neurons with expression of KV4.2W362F: molecular dissection of IA.
pubmed:affiliation
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.