Cytosolic Ca²⁺ gradients triggering unidirectional fluid secretion from exocrine pancreas

Abstract

EXOCRINE gland cells secrete Cl^–-rich fluid when stimulated by neurotransmitters or hormones¹. This is generally ascribed to a rise in cytosolic Ca²⁺ concentration² ([Ca²⁺]_i), which leads to activation of Ca²⁺-dependent ion channels^3,4. A precise understanding of Cl^- secretion from these cells has been hampered by a lack of knowledge about the spatial distribution of the Ca²⁺ signal and of the Ca²⁺-dependent ion channels in the secreting epithelial cells⁴. We have now used the whole-cell patch-clamp method and digital imaging5 of [Ca²⁺]_i to examine the response of rat pancreatic acinar cells to acetylcholine. We found a polarization of [Ca²⁺]_i elevation and ion channel activation, and suggest that this comprises a novel 'push–pull' mechanism for unidirectional Cl^- secretion. This mechanism would represent a role for cytosolic Ca²⁺ gradients in cellular function. The cytosolic [Ca²⁺]_i gradients and oscillations of many other cells² could have similar roles.