Mechanism of milk secretion: milk composition in relation to potential difference across the mammary epithelium.

1. In conscious lactating goats a significant correlation was found between blood-milk potential difference (p.d.) and milk [lactose] such that in goats with a lower milk [lactose], milk was more negative with respect to blood.2. When mannose was substituted for glucose in the substrate mixture of isolated perfused goat mammary glands, milk yield and milk [lactose] fell while milk [Na] and [K] increased; in parallel experiments the blood-milk p.d. changed such that milk became more negative with respect to blood. These changes were reversed following the addition of glucose.3. When milk was made hypertonic by the addition of hyperosmotic sucrose or lactose solutions, water entered milk osmotically and milk became electrically less negative or even positive with respect to blood in goats, cows and guinea-pigs.4. No effect on p.d. was apparent following the addition of isosmotic sucrose to milk in goats.5. When milk was held in the teat of goats by a pneumatic cuff around the base of the teat, no effect on p.d. was apparent when hyperosmotic sucrose was introduced into this teat pouch.6. It is suggested that waterflow-induced potentials (the streaming potential and the transport number effect) can be induced across the mammary epithelium.7. In goats exogenous oxytocin lowered milk [lactose] and blood-milk p.d. became less negative with respect to blood.8. In non-lactating and mastitic glands of goats the blood-milk p.d. was within 0.5-2.5 mV of zero.9. The effects of oxytocin, and the low p.d. in non-lactating and mastitic glands, are compatible with the view that in such circumstances there is a paracellular pathway across the mammary epithelium which partially short-circuits the two sides.10. It is suggested that, with water being drawn osmotically into milk to dilute newly formed lactose, waterflow-induced potentials may be responsible for establishing the normal p.d. across the apical membrane of the secretary cell, thereby keeping milk [K] and [Na] lower than in intracellular fluid.