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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2010-4-7
pubmed:abstractText
The rapidly activating and inactivating voltage-gated K(+) (Kv) current, I(A), is broadly expressed in neurons and is a key regulator of action potential repolarization, repetitive firing, backpropagation (into dendrites) of action potentials, and responses to synaptic inputs. Interestingly, results from previous studies on a number of neuronal cell types, including hippocampal, cortical, and spinal neurons, suggest that macroscopic I(A) is composed of multiple components and that each component is likely encoded by distinct Kv channel alpha-subunits. The goals of the experiments presented here were to test this hypothesis and to determine the molecular identities of the Kv channel alpha-subunits that generate I(A) in cortical pyramidal neurons. Combining genetic disruption of individual Kv alpha-subunit genes with pharmacological approaches to block Kv currents selectively, the experiments here revealed that Kv1.4, Kv4.2, and Kv4.3 alpha-subunits encode distinct components of I(A) that together underlie the macroscopic I(A) in mouse (male and female) cortical pyramidal neurons. Recordings from neurons lacking both Kv4.2 and Kv4.3 (Kv4.2(-/-)/Kv4.3(-/-)) revealed that, although Kv1.4 encodes a minor component of I(A), the Kv1.4-encoded current was found in all the Kv4.2(-/-)/Kv4.3(-/-) cortical pyramidal neurons examined. Of the cortical pyramidal neurons lacking both Kv4.2 and Kv1.4, 90% expressed a Kv4.3-encoded I(A) larger in amplitude than the Kv1.4-encoded component. The experimental findings also demonstrate that the targeted deletion of the individual Kv alpha-subunits encoding components of I(A) results in electrical remodeling that is Kv alpha-subunit specific.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
7
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5092-101
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Molecular dissection of I(A) in cortical pyramidal neurons reveals three distinct components encoded by Kv4.2, Kv4.3, and Kv1.4 alpha-subunits.
pubmed:affiliation
Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural