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Paradoxical block of the Na + ‐Ca 2+ exchanger by extracellular protons in guinea‐pig ventricular myocytes
Author(s) -
Egger Marcel,
Niggli Ernst
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.t01-1-00353.x
Subject(s) - extracellular , intracellular ph , chemistry , biophysics , intracellular , myocyte , cytosol , sodium calcium exchanger , ion transporter , calcium , sodium , biochemistry , biology , endocrinology , membrane , enzyme , organic chemistry
1 The Na + ‐Ca 2+ exchange is a major pathway for removal of cytosolic Ca 2+ in cardiac myocytes. It is known to be inhibited by changes of intracellular pH that may occur, for example, during ischaemia. In the present study, we examined whether extracellular protons (pH o ) can also affect the cardiac exchange. 2 Na + ‐Ca 2+ exchange currents ( I Na‐Ca ) were recorded from single adult guinea‐pig ventricular myocytes in the whole‐cell voltage‐clamp configuration while [Ca 2+ ] i was simultaneously imaged with fluo‐3 and a laser‐scanning confocal microscope. To activate I Na‐Ca , intracellular Ca 2+ concentration jumps were generated by laser flash photolysis of caged Ca 2+ (DM‐nitrophen). 3 Exposure of the cell to moderately and extremely acidic conditions (pH o 6 and 4) was accompanied by a decrease of the peak I Na‐Ca to 70 % and less than 10 %, respectively. The peak I Na‐Ca was also inhibited to about 45 % of its initial value by increasing pH o to 10. The largest I Na‐Ca was found at pH o ≈ 7·6. 4 Simultaneous measurements of [Ca 2+ ] i and I Na‐Ca during partial proton block of the Na + ‐Ca 2+ exchanger revealed that the exchange current was more inhibited by acidic pH o than the rate of Ca 2+ transport. This observation is consistent with a change in the electrogenicity of the Na + ‐Ca 2+ exchange cycle after protonation of the transporter. 5 We conclude that both extracellular alkalinization and acidification affect the Na + ‐Ca 2+ exchanger during changes of pH o that may be present under pathophysiological conditions. During both extreme acidification or alkalinization the Na + ‐Ca 2+ exchanger is strongly inhibited, suggesting that extracellular protons may interact with the Na + ‐Ca 2+ exchanger at multiple sites. In addition, the electrogenicity and stoichiometry of the Na + ‐Ca 2+ exchange may be modified by extracellular protons.