Red cell volume regulation: the pivotal role of ionic strength in controlling swelling-dependent transport systems

• Published in: Biochimica et biophysica acta Vol. 1075; no. 2; pp. 169 - 180
• Main Authors: Motais, R., Guizouarn, H., Garcia-Romeu, F.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 10.10.1991; Elsevier
• Subjects: Ammonium Chloride; Animals; Biological and medical sciences; Biological Transport; Cell Membrane Permeability - drug effects; Cell physiology; Cell volume regulation; Choline transport; Cyclic AMP - pharmacology; DIDS; Erythrocyte Membrane - drug effects; Erythrocyte Membrane - physiology; Erythrocyte Volume - drug effects; Erythrocyte Volume - physiology; Fundamental and applied biological sciences. Psychology; Hydrogen-Ion Concentration; Hypotonic Solutions; Ionic strength; Isoproterenol - pharmacology; Isotonic Solutions; K pathway; Membrane and intracellular transports; Molecular and cellular biology; Osmolar Concentration; Sodium Chloride; Taurine transport; Trout; Trout erythrocyte; Urea; K pathway; dcs, dry cell solid; Taurine transport; Trout erythrocyte; DIDS; Ionic strength; VDR, volume decrease response; Cell volume regulation; Choline transport; Taurine; Red blood cell; Osmoregulation; Coupled transport; Oncorhynchus mykiss; Mechanism; Vertebrata; Sodium; Membrane transport; Pisces; Choline; Proton; Cell volume
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/0304-4165(91)90248-F

A volume increase of trout erythrocytes can be induced either by β-adrenergic stimulation of a Na +/H + antiport in an isotonic medium (isotonic swelling) or by suspending red cells in an hypotonic medium (hypotonic swelling). In both cases cells regulate their volume by a loss of osmolytes via specific pathways. After hypotonic swelling several volume-dependent pathways were activated allowing K +, Na +, taurine and choline to diffuse. All these pathways were fully inhibited by furosemide and inhibitors of the anion exchanger (DIDS, niflumic acid), and the K + loss was mediated essentially via a ‘Cl −-independent’ pathway. After isotonic swelling, the taurine, choline and Na + pathways were practically not activated and the K + loss was strictly ‘Cl −-dependent’. Thus cellular swelling is a prerequisite for activation of these pathways but, for a given volume increase, the degree of activation and the degree of anion-dependence of the K + pathway depend on the nature of the stimulus, whether hormonal or by reduction of osmolality. It appears that the pattern of the response induced by hormonal stimulation is not triggered by either cellular cAMP (since it can be reproduced in the absence of hormone by isotonic swelling in an ammonium-containing saline) or by the tonicity of the medium in which swelling occurs since after swelling in an isotonic medium containing urea, the cells adopt the regulatory pattern normally observed after hypotonic swelling. We demonstrated that the stimulus is the change in cellular ionic strength induced by swelling: when ionic strength drops, the cells adopt the hypotonic swelling pattern; when ionic strength increases, the isotonic swelling pattern is activated. To explain this modulating effect of ionic strength a speculative model is proposed, which also allows the integration of two further sets of experimental results: (i) all the volume-activated transport systems are blocked by inhibitors of the anion exchanger and (ii) a Cl −-dependent, DIDS-sensitive K + pathway can be activated in static volume trout red cells (i.e., in the absence of volume increase) by the conformational change of hemoglobin induced by the binding of O 2 or CO to the heme.