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Titolo:
REGULATION OF CARDIAC CA2-NUCLEOTIDES UNDER NORMAL AND SIMULATED ISCHEMIC CONDITIONS( RELEASE CHANNEL (RYANODINE RECEPTOR) BY CA2+, H+, MG2+, AND ADENINE)
Autore:
XU L; MANN G; MEISSNER G;
Indirizzi:
UNIV N CAROLINA,DEPT BIOCHEM & BIOPHYS CHAPEL HILL NC 27599 UNIV N CAROLINA,DEPT BIOCHEM & BIOPHYS CHAPEL HILL NC 27599 UNIV N CAROLINA,DEPT PHYSIOL CHAPEL HILL NC 27599
Titolo Testata:
Circulation research
fascicolo: 6, volume: 79, anno: 1996,
pagine: 1100 - 1109
SICI:
0009-7330(1996)79:6<1100:ROCCUN>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
MUSCLE SARCOPLASMIC-RETICULUM; CALCIUM-RELEASE; CONTRACTILE FAILURE; RAT-HEART; CA-2+; REPERFUSION; TRANSIENTS; VESICLES; COMPLEX; INJURY;
Keywords:
EXCITATION-CONTRACTION COUPLING; ISCHEMIA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
34
Recensione:
Indirizzi per estratti:
Citazione:
L. Xu et al., "REGULATION OF CARDIAC CA2-NUCLEOTIDES UNDER NORMAL AND SIMULATED ISCHEMIC CONDITIONS( RELEASE CHANNEL (RYANODINE RECEPTOR) BY CA2+, H+, MG2+, AND ADENINE)", Circulation research, 79(6), 1996, pp. 1100-1109

Abstract

In myocardial ischemia, pH(i) and [ATP] fall, whereas the free [Ca2+]and [Mg2+] rise. The effects of these changes on cardiac Ca2+ releasechannel (ryanodine receptor) activity were investigated in [H-3]ryanodine binding and single-channel measurements, using isolated membrane and purified channel preparations. In the absence of the two channel ligands Mg2+ and ATP, cardiac Ca2+ release channels were half-maximallyactivated at pH 7.4 by approximate to 4 mu mol/L cytosolic Ca2+ and half-maximally inhibited by approximate to 9 mmol/L cytosolic Ca2+. Regulation of channel activity by Ca2+ was modulated by Mg2+ and ATP. Single-channel activities were more sensitive to a change of cytosolic pHthan SR lumenal pH. Reduction in lumenal and/or cytosolic pH from 7.3to 6.5 and 6.0 resulted in decreased single-channel activities without a change in single-channel conductance. [H-3]Ryanodine binding measurements also indicated that acidosis impairs cardiac Ca2+ release channel activity. Mg2+ and adenine nucleotide concentrations regulated theextent of inhibition and the Ca2+ dependence of binding. In the presence of 5 mmol/L Mg2+ and 5 mmol/L beta, gamma-methyleneadenosine 5'-triphosphate (AMPPCP, a nonhydrolyzable ATP analogue), the free [Ca2+] for half;maximal [H-3]ryanodine binding was increased from 1.9 mu mol/Lat pH 7.3 to 36 mu mol/L at pH 6.5 and to 89 mu mol/L at pH 6.2. These results suggest that ionic and metabolic changes that might be expected to affect sarcoplasmic reticulum Ca2+ release channel activity in ischemic myocardium include an altered Ca2+ sensitivity of the channel, a fall in pH, and a loss of the high-energy adenine nucleotide pool,leading to an increased inhibition by Mg2+.

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Documento generato il 04/12/20 alle ore 16:44:44