Biomaterial Database

Paradoxical block of the Na+-Ca2+ exchanger by extracellular protons in guinea-pig ventricular myocytes. 2000

M Egger, and E Niggli

Department of Physiology, University of Bern, Buhlplatz 5, CH-3012 Bern, Switzerland.

1. The Na+-Ca2+ exchange is a major pathway for removal of cytosolic Ca2+ 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 (pHo) can also affect the cardiac exchange. 2. Na+-Ca2+ exchange currents (INa-Ca) were recorded from single adult guinea-pig ventricular myocytes in the whole-cell voltage-clamp configuration while [Ca2+]i was simultaneously imaged with fluo-3 and a laser-scanning confocal microscope. To activate INa-Ca, intracellular Ca2+ concentration jumps were generated by laser flash photolysis of caged Ca2+ (DM-nitrophen). 3. Exposure of the cell to moderately and extremely acidic conditions (pHo 6 and 4) was accompanied by a decrease of the peak INa-Ca to 70 % and less than 10 %, respectively. The peak INa-Ca was also inhibited to about 45 % of its initial value by increasing pHo to 10. The largest INa-Ca was found at pHo approximately 7.6. 4. Simultaneous measurements of [Ca2+]i and INa-Ca during partial proton block of the Na+-Ca2+ exchanger revealed that the exchange current was more inhibited by acidic pHo than the rate of Ca2+ transport. This observation is consistent with a change in the electrogenicity of the Na+-Ca2+ exchange cycle after protonation of the transporter. 5. We conclude that both extracellular alkalinization and acidification affect the Na+-Ca2+ exchanger during changes of pHo that may be present under pathophysiological conditions. During both extreme acidification or alkalinization the Na+-Ca2+ exchanger is strongly inhibited, suggesting that extracellular protons may interact with the Na+-Ca2+ exchanger at multiple sites. In addition, the electrogenicity and stoichiometry of the Na+-Ca2+ exchange may be modified by extracellular protons.

UI	MeSH Term	Description	Entries
D007424	Intracellular Fluid	The fluid inside CELLS.	Fluid, Intracellular,Fluids, Intracellular,Intracellular Fluids
D008564	Membrane Potentials	The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).	Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D002021	Buffers	A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer.	Buffer
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D005110	Extracellular Space	Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall.	Intercellular Space,Extracellular Spaces,Intercellular Spaces,Space, Extracellular,Space, Intercellular,Spaces, Extracellular,Spaces, Intercellular
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006352	Heart Ventricles	The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.	Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right
D006863	Hydrogen-Ion Concentration	The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH	pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D000143	Acids	Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. (Grant & Hackh's Chemical Dictionary, 5th ed)	Acid