Letter to the Editor

Abstract

Palmer et al. (2011) have made a detailed study of the purinergic regulation of K+ and Na+ transport by immortalized human mammary epithelial cell monolayers and provide evidence for differential effects of agonists at the apical and basolateral membranes. The authors claim that their cell culture system is a model for mammary ductal epithelial cells. Furthermore, they suggest that the results of the study help explain how mammary ductal epithelial cells modulate the ion content of milk. There are several points which need to be addressed before these conclusions can be generally accepted. Firstly, Palmer et al. (2011) claim that the mammary cells used in their study are ductal in origin. However, they provide no firm evidence to support this assumption, thus there is a possibility that the cells may indeed be alveolar. Thus, Palmer et al. (2011) need to establish whether or not the cells synthesize and secrete caseins and/or lactose when cultured in the presence of lactogenic hormones. Secondly, the authors show that purinergic agonists increase cytosolic Ca2+ which in turn stimulates Ca2+-activated K+ channels. In contrast, it has been reported that ATP has no effect on cytosolic Ca2+ in acini freshly isolated from the lactating mouse mammary gland (Sudlow & Burgoyne, 1997). In this connection, Katoh et al. (2001) have shown that ATP causes a large transient increase in cytosolic Ca2+ in bovine mammary epithelial cells; however, the effect of ATP is almost abolished by culturing cells in the presence of lactogenic hormones. In view of this, it is incumbent upon Palmer et al. (2011) to repeat their study with cells cultured in the presence of a precisely defined cocktail of lactogenic hormones such as dexamethasone, insulin and prolactin. Thirdly, Palmer et al. (2011) fail to take cognisance of a long-standing model of milk ion secretion initially proposed by Linzell & Peaker (1971a). The most salient feature of the model is that the primary secretion is not markedly modified by the ductal epithelial cells. Indeed, Linzell & Peaker (1971b) reported that the apical pole of goat mammary ductal epithelial cells in vivo is relatively impermeable to both Na+ and K+. Palmer et al. (2011) need to reconcile their data with the more physiologically relevant findings of Linzell & Peaker (1971b). Fourthly, the major osmolyte in milk is lactose, therefore experimentalists wishing to use cultured monolayers as a model to study the function of mammary cells (whether alveolar or ductal cells) should at least consider bathing the apical aspect of the epithelial cells with a solution containing lactose at a concentration similar to that found in milk. Such an approach will make the results more physiologically relevant. In this regard, Quesnell et al. (2007) have shown that the barrier properties of cultured bovine epithelial cell monolayers are governed by the electrolyte content of the solution bathing the apical aspect. Thus, monolayers whose apical aspect is exposed to a low-ionic strength medium, similar to that of milk, develop a greater trans-epithelial electrical resistance. It is imperative that caution must be exercised when interpreting the findings made with cultured cells in relation to the function of a highly regulated and complex epithelium such as the lactating mammary gland.