Editorial 1 1 D oes the Na , K pump current undergo remodeling in atrial fibrillation ?

See article by Workman et al. [1] (pages 593–602) in energy to transporters that do not use ATP as an energy 1 21 1 1 this issue. source, such as the Na ,Ca exchanger, the Na ,H 1 1 2 The sodium pump current has been the subject of many exchanger, the Na ,K ,2Cl cotransporter, the 1 2 1 studies, but information on human cardiac tissue is lacking. Na ,HCO cotransporter, and the Na ,glucose and 3 1 This gap has been filled by a paper published in this issue Na ,amino acid cotransporters [3]. 1 in which Workman, Kane and Rankin [1] describe the Important biophysical characteristics of the Na pump 1 maximal capacity and functional characteristics of the are its maximum capacity, the sensitivity to [K ] and e 1 1 1 Na ,K pump current (I ) in atrial cells from patients with [Na ] , its voltage dependence and its sensitivity to cardiac p i and without chronic atrial fibrillation (AF). The main glycosides. These properties differ among species, among conclusions are that the pump current contributes to the tissues and among regions in the same tissue. In guinea pig 1 1 resting potential and the duration of the action potential. atrial cells, the maximum hydrolytic activity of Na ,K 1 1 Sensitivity to the external K concentration, [K ] , and ATPase is only 33% of that of ventricular cells [4]. This e the voltage dependence of the pump do not change in AF. lower density of pump sites in atrial cells has been The authors conclude that I is not involved in AF-induced confirmed in a study of protein expression and has been p electrophysiological remodeling in patients. Before discussuggested to be the reason for the lower resting membrane sing these interesting findings it seems worthwhile to potential and the higher sensitivity to pump blockade in provide some general information on the characteristics of atrial cells [4,5]. 1 1 the Na ,K pump [2]. The sensitivity to ions and drugs depends on the 1 1 The Na ,K pump is essential to cell survival. (1) By constitution of the isoforms [6]. The sodium pump is a 1 1 producing K and Na gradients between the intraand heterodimer consisting of a catalytic a-subunit and an extracellular medium the pump is of primordial importance associated glycoprotein, the b-subunit. Three a-isoforms in the generation of the resting membrane potential and the have been described. In the human heart the pump consists 1 action potential upstroke. Since the number of Na and of 55% a1, 18% a2 and 27% a3, and b1. The sensitivity 1 K ions transported is three to two, the pump also of these isoforms to ions and drugs can be expressed by generates an outward current. Its contribution as a current the affinity or the half maximum (K ) constants. In the 0.5 1 to the resting potential is minor, but it modulates pacehuman heart the affinity for [K ] is 0.9, 1.3 and 0.9 mM, e maker activity and action potential duration. The effect on respectively, for the three isoforms; the sensitivity to 1 29 the repolarization process is related to the high electrical [Na ] is 8.2, 12.8 and 24.7 mM and to ouabain 19310 , i 29 29 resistance during the plateau of the cardiac action potential. 37310 and 14310 M. The affinity values demon1 1 Block of the pump causes action potential lengthening and strate that [Na ] is the main regulator of the Na pump, i 1 symptoms comparable to the LQT syndrome. (2) By since the actual values of [Na ] are close to the K of i 0.5 1 1 generating a Na gradient the pump provides potential ATPase. For external K , the K value is much smaller 0.5 than the concentration encountered in the extracellular 1 medium, indicating that the K sensitive site is practically *Tel.: 132-16-402-823; fax: 132-16-347-139. E-mail address: [email protected] (E. Carmeliet). saturated. The isoform constitution is important in de-