Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1992-9-2
pubmed:abstractText
1. The effects of complete metabolic inhibition on excitation-contraction coupling in heart were studied by exposing patch-clamped guinea-pig ventricular myocytes, loaded via the patch pipette with the Ca2+ indicator Fura-2 (0.1 mM), to carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP, 1 microM) and 2-deoxyglucose (2-DG, 10 mM) while simultaneously recording membrane current, Fura-2 fluorescence, and cell motion. The patch pipette solution contained Cs+ and TEA (tetraethylammonium) to partially block K+ currents. 2. During voltage clamps from a holding potential of -40 mV to a test potential of 0 mV, complete metabolic inhibition decreased the Ca2+ current (ICa), activated the ATP-sensitive K+ current, modestly elevated diastolic [Ca2+]i and markedly reduced the [Ca2+]i transient without altering its voltage dependence. Active shortening was impaired and diastolic cell length decreased prior to large increases in diastolic [Ca2+]i, consistent with rigor induced by ATP depletion. Return of the [Ca2+]i transient to baseline and relaxation upon repolarization were also delayed. 3. Despite the depression of the peak [Ca2+]i transient induced by membrane depolarization during metabolic inhibition, the [Ca2+]i transient induced by a rapid exposure to 5 mM-caffeine was greater than control. The Na(+)-Ca2+ exchange current during the caffeine-induced [Ca2+]i transient was not affected by metabolic inhibition. 4. [Ca2+]i transients depressed by metabolic inhibition could be enhanced by augmenting ICa with elevated [Ca2+]o (10 mM) and Bay K 8644 (5 microM). 5. To study the relationship between the magnitude of ICa and the amplitude of the [Ca2+]i transient, ICa was modulated either by (a) voltage clamping the cell to different membrane potentials at constant [Ca2+]o or by (b) rapidly altering [Ca2+]o immediately prior to a voltage clamp to a fixed membrane potential. Under control conditions, the relationship between the size of ICa and the magnitude of the [Ca2+]i transient was the same whether ICa was modulated by altering membrane potential or [Ca2+]o, suggesting that membrane potential does not significantly modulate the Ca(2+)-induced Ca2+ release mechanism of cardiac excitation-contraction coupling. 6. After metabolic inhibition, however, the same ICa released less Ca2+ than under control conditions, consistent with some impairment of the Ca2+ release mechanism. 7. These results suggest that under conditions in which excitability is maintained by controlling membrane voltage and minimizing metabolically sensitive K+ currents, the decreased [Ca2+]i transient observed during metabolic inhibition severe enough to induce rigor is caused primarily by depression of ICa and not by depletion of intracellular Ca2+ stores. Additional factors also modestly hinder Ca2+ release from intracellular stores during metabolic inhibition.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-1984866, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2158146, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2158147, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2311000, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2410609, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2434495, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2445968, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2446391, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2457095, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2475607, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2512370, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2543067, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2581508, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-25957, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2600854, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2614727, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2720061, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2723059, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2726431, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2750887, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2795481, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-2998207, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-3162323, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-3360456, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-3413129, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-3552284, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-3656151, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-3838314, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-3878160, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-3958986, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-6270629, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-627548, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-6371254, http://linkedlifedata.com/resource/pubmed/commentcorrection/1822531-7131563
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3751
pubmed:author
pubmed:issnType
Print
pubmed:volume
443
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
371-86
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Mechanisms of excitation-contraction coupling failure during metabolic inhibition in guinea-pig ventricular myocytes.
pubmed:affiliation
Division of Cardiology, UCLA School of Medicine 90024.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't