Linked Life Data

9120601

Source:http://linkedlifedata.com/resource/pubmed/id/9120601

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-4-22
pubmed:abstractText
ATP-modulated K+ channels play an important role in regulating membrane excitability during metabolic stress. To characterize such K+ channels from the human brain, single channel currents were studied in excised inside-out patches from freshly dissociated human neocortical neurons. Three currents that were sensitive to physiological concentrations of ATP and selectively permeable to K+ were identified. One of these currents had a unitary conductance of approximately 47 pS and showed a strong inward rectification with symmetric K+ concentrations across the membrane. This K+ current was inhibited by ATP in a concentration-dependent manner with an IC50 (half-inhibition of channel activity) of approximately 130 microM. Channel activity also was suppressed by ADP, non-hydrolyzable ATP analogue AMP-PNP, and sulfonylurea receptor/ channel blocker glibenclamide. The second K+ current had a unitary conductance of approximately 200 pS and showed a weak inward rectification. Similarly, this current was inhibited by ATP (IC50 = 350 microM), AMP-PNP, and glibenclamide. Unlike the small-conductance ATP-inhibitable K+ channel (S-KATP), activation of this large-conductance K+ channel (L-KATP) required the presence of micromolar concentration of Ca2+ in the internal solution, but charybdotoxin did not inhibit this channel. The third K+ current was also Ca2+ dependent and had a large conductance (approximately 280 pS). It was inhibited by external charybdotoxin, iberiotoxin, and tetraethylammonium. In contrast to the other two KATP channels, ATP enhanced channel open-state probability and unitary conductance, and glibenclamide at concentration of 10-20 microM had no inhibitory effect on this current. K+ channels that have single-channel and pharmacological properties similar to these three human ATP-modulated K+ channels also were observed in experiments on rat neocortical neurons. These results therefore indicate that KATP channels are expressed in human neocortical neurons, and two distinct KATP channels (S-KATP and L-KATP) exist in the human and rat neurons. The observation that ATP at different concentrations modulates different K+ channels suggests that metabolic rate may be continuously sensed in neurons with resulting alterations in neuronal membrane excitability.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3077
pubmed:author
pubmed:issnType
Print
pubmed:volume
77
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
93-102
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Modulation of K+ channels by intracellular ATP in human neocortical neurons.
pubmed:affiliation
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't