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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-7-8
pubmed:abstractText
The Na(+)-K+ pump is a consumer of intracellular ATP. We therefore examined whether blockade of the Na(+)-K+ pump by cardiac glycosides could inhibit ATP-sensitive K+ (KATP) channels and prolong the action potential duration (APD) of the guinea-pig ventricular muscles perfused with Tyrode's solution via the coronary artery and stimulated at 3 Hz. The metabolic inhibition (MI) achieved by application of 0.1 microM carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (a mitochondrial uncoupler) shortened the APD in a time-dependent manner. When dihydroouabain (DHO, 5 microM) was introduced 5 min but not 10 min after introduction of MI, the APD shortening was significantly attenuated. Application of glibenclamide (1 microM), a blocker of KATP channels, introduced both 5 and 10 min after MI also alleviated the APD shortening: DHO did not alleviate the APD shortening effect produced by cromakalim (5 microM), a KATP-channel opener. In separate experiments using whole-cell patch-clamp techniques, we found that this concentration of DHO (5 microM) depressed the Na(+)-K+ pump current of the guinea-pig ventricular myocytes from 210 to 100 pA (at 0 mV) or by 49.5%. We conclude that, during early phase (approximately 5 min) of MI, the APD shortening mostly results from the activation of KATP channels, and that even a approximately 50% inhibition of the Na(+)-K+ pump by DHO leads to the blockade of KATP channels and eventual lengthening of the APD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-2828
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
533-42
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Inhibition of Na(+)-K+ pump alleviates the shortening of action potential duration caused by metabolic inhibition via blockade of KATP channels in coronary perfused ventricular muscles of guinea-pigs.
pubmed:affiliation
Department of Physiology, Oita Medical University, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't