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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-1-29
pubmed:abstractText
We studied the phenomenon of cumulative inactivation in the voltage-dependent K+ channels of the Shaker-related subfamily Kv1 cloned from rat brain and expressed in Xenopus oocytes. In Kv1.4, repetitive stimulations at intervals shorter than 20 s produce cumulative inactivation even for brief stimuli that elicit K+ currents which do not show any significant decline during the depolarising pulse. These effects are absent or greatly reduced in the clones Kv1.1, Kv1.3, Kv1.5 and Kv1.6, and in the deletion mutant Kv1.4-delta-110, characterised by lack of "fast" (N-type) inactivation. We find that the inactivation caused by a single pulse increases after the pulse while the channels deactivate, and subsides with two time constants, indicating the existence of (at least) two inactivated states: IS, with a slow recovery kinetics and IF, with faster kinetics. In the simplest kinetic scheme accounting for our observations, IF is coupled sequentially to the open state O, while IS can be reached at a fast rate both from IF and from a pre-open, activated state, A, that is in fast equilibrium with O. The accumulation of long-lasting inactivation during the repolarisation is favoured by the prolongation of the lifetime of activated states due to the presence of IF. This explains the smaller accumulation effect observed in channels lacking fast inactivation. The physiological implications of these findings suggest how different channels of the Kv1 subfamily can affect differently the firing behaviour of neurones.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0014-4819
pubmed:author
pubmed:issnType
Print
pubmed:volume
110
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
401-12
pubmed:dateRevised
2009-11-11
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Accumulation of long-lasting inactivation in rat brain K(+)-channels.
pubmed:affiliation
Istituto di Cibernetica e Biofisica, CNR, Genoa, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't