The squid preparation as a general model for ionic and metabolic Na+/Ca2+ exchange interactions -: Physiopathological implications

被引:5
作者
Dipolo, R.
Beauge, L.
机构
[1] Inst Venezolano Invest Cient, Lab Fisiol Celular, Ctr Biofis & Bioquim, Caracas 1020A, Venezuela
[2] Marine Biol Lab, Woods Hole, MA 02543 USA
[3] Inst Invest Med M&M Ferreyra, Lab Biofis, RA-5000 Cordoba, Argentina
来源
SODIUM-CALCIUM EXCHANGE AND THE PLASMA MEMBRANE CA2+-ATPASE IN CELL FUNCTION: FIFTH INTERNATIONAL CONFERENCE | 2007年 / 1099卷
关键词
sodium-calcium exchange; ionic and metabolic regulation; squid axons; cellular ischemia;
D O I
10.1196/annals.1387.049
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We propose an integrated kinetic model for the squid nerve Na+/Ca2+ exchanger based on experimental evidences obtained in dialyzed axons. This model satisfactorily explains the interrelationship between ionic (Na-i(+)-H-i(+)-Ca-i(2+)) and metabolic (ATP, phosphoarginine (PA)) regulation of the exchanger. Data in dialyzed axons show that the Ca-i-regulatory site located in the large intracellular loop plays a central role in the modulation by ATP by antagonizing the inhibitory Na-i(+)-H-i(+) synergism. We have used the Na-o/Na-i exchange mode to unequivocally measure the affinity of the Cai-regulatory site. This allowed us to separate Ca-i-regulatory from Ca-i-transport sites and to estimate their respective affinities. In this work we show for the first time that under conditions of saturation of the Ca-i-regulatory site (10 mu M Ca-i(2+) pH(i) 8.0), ATP have no effect on the Cai-transport site. In addition, we have expanded our equilibrium kinetic model of ionic and metabolic interactions to a complete exchange cycle (circular model). This model, in which the Cai-regulatory site plays a central role, accounts for the decrease in Na-i inactivation, at high pH(i), high Ca-i(2+) and MgATP. Furthermore, the model also predicts the net Ca2+ movements across the exchanger based on the exchanger complexes redistribution both during physiological and pathological conditions (ischemia).
引用
收藏
页码:135 / 151
页数:17
相关论文
共 25 条
[1]  
BERS D, 1991, DEV CARDIAC VASCULAR, V122
[2]  
Blaustein M. P., 1977, AM J PHYSIOL, V1, P165
[3]   Sodium calcium exchange: Its physiological implications [J].
Blaustein, MP ;
Lederer, WJ .
PHYSIOLOGICAL REVIEWS, 1999, 79 (03) :763-854
[4]   Sodium/calcium exchanger:: Influence of metabolic regulation on ion carrier interactions [J].
Dipolo, R ;
Beaugé, L .
PHYSIOLOGICAL REVIEWS, 2006, 86 (01) :155-203
[5]   Phosphoarginine regulation of the squid nerve Na+/Ca2+ exchanger:: metabolic pathway and exchanger-ligand interactions different from those seen with ATP [J].
DiPolo, R ;
Berberián, G ;
Beaugé, L .
JOURNAL OF PHYSIOLOGY-LONDON, 2004, 554 (02) :387-401
[6]   MgATP counteracts intracellular proton inhibition of the sodium-calcium exchanger in dialysed squid axons [J].
DiPolo, R ;
Beaugé, L .
JOURNAL OF PHYSIOLOGY-LONDON, 2002, 539 (03) :791-803
[7]   ASYMMETRICAL PROPERTIES OF THE NA-CA EXCHANGER IN VOLTAGE-CLAMPED, INTERNALLY DIALYZED SQUID AXONS UNDER SYMMETRICAL IONIC CONDITIONS [J].
DIPOLO, R ;
BEAUGE, L .
JOURNAL OF GENERAL PHYSIOLOGY, 1990, 95 (05) :819-835
[8]   REGULATION OF NA-CA EXCHANGE - AN OVERVIEW [J].
DIPOLO, R ;
BEAUGE, L .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1991, 639 :100-111
[9]  
DIPOLO R, 1990, INTRACELLULAR CALCIU, P381
[10]  
DOERING AE, 1993, J PHYSIOL-LONDON, V466, P481