Cytosolic Ca2+ gradients triggering unidirectional fluid secretion from exocrine pancreas

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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 channels3,4. 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.