Abstract
Mammary glands are physiologically active in female mammals only during nursing. Immediately after weaning, most lactation-related genes are downregulated and milk production ceases. In our previous study, we have detected an inwardly rectifying potassium channel (Kir) 2.1-like current in mammary secretory (MS) cells freshly isolated from lactating mice. This current is highly sensitive to external Ba2+. The potassium permeability of the Kir channels may contribute to the secretion and/or preservation of ions in milk. We hypothesized that the functions of the Kir channels in MS cells are regulated after weaning. To test this hypothesis, we examined the effect of forced weaning on the Ba2+-sensitive Kir current and Kir2.1 expression in the mouse mammary glands. Twenty-four hours after weaning, the lumina of mammary acini were histologically enlarged by milk accumulation. The whole-cell patch-clamp analyses showed that the Ba2+-sensitive Kir current in the post-weaning MS cells was smaller than in the lactating MS cells. The inward conductances of the current in the lactating and post-weaning cells were 4.25 ± 0.77 and 0.93 ± 0.34 nS, respectively. Furthermore, real-time PCR and Western blot analyses showed that Kir2.1 mRNA and protein expression decreased in the post-weaning mammary gland (mRNA, 90% reduction; protein, 47% reduction). Moreover, the local milk accumulation caused by teat sealing decreased Kir conductance in MS cells (2.74 ± 0.45 and 0.36 ± 0.27 nS for control and sealed mammary glands, respectively). This was concomitant with the reduction in the Kir2.1 mRNA expression. Our results suggest that milk stasis after weaning immediately decreases the Kir conductance in MS cells. This decrease in the Kir conductance may be partly caused by the reduction in the Kir2.1 mRNA and protein expression. These alterations during the post-weaning period may be involved in the cessation of ion secretion and/or preservation in the milk.
Highlights
The mammary gland is an exocrine gland that functions only during the lactation period in female mammals
When lactating mammary secretory (MS) cells were perfused with K-glutamate-rich pipette solution and NaCl-rich bath solution, the whole-cell currents displayed the inward rectification at the potentials more negative than the equilibrium potential of K+ (EK −86 mV) (Fig 2B)
To demonstrate the alteration of Kir current amplitude clearly, Ba2+ (10−4 M)-sensitive Kir current in MS cell was determined under the NMDG-glutamate-rich conditions (Na+ and Cl− in the bath solution were mostly replaced by NMDG and glutamate, respectively)
Summary
The mammary gland is an exocrine gland that functions only during the lactation period in female mammals. Mammary acini develop on the mammary ducts during pregnancy, and acinar cells differentiate into secretory cells. The milk produced by the secretory cells is stored in the lumina and ejected from the teats in response to suckling stimuli, providing nutrition to the pups. The mammary glands stop milk production and begin to involute within a few days after weaning [1]. The mechanisms by which lactation stops after weaning are not clear. To understand these mechanisms in detail, we focused on the alterations in ion permeabilities of MS cells after weaning
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