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Macula Densa Cell Signaling Involves ATP Release through a Maxi Anion Channel

Phillip Darwin Bell, Jean-Yves Lapointe, Ravshan Sabirov, Seiji Hayashi, Janos Peti-Peterdi, Ken-ichi Manabe, Gergely Kovacs and Yasunobu Okada
Proceedings of the National Academy of Sciences of the United States of America
Vol. 100, No. 7 (Apr. 1, 2003), pp. 4322-4327
Stable URL: http://www.jstor.org/stable/3148784
Page Count: 6
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Macula Densa Cell Signaling Involves ATP Release through a Maxi Anion Channel
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Abstract

Macula densa cells are unique renal biosensor cells that detect changes in luminal NaCl concentration ([ NaCl]L) and transmit signals to the mesangial cell/afferent arteriolar complex. They are the critical link between renal salt and water excretion and glomerular hemodynamics, thus playing a key role in regulation of body fluid volume. Since identification of these cells in the early 1900s, the nature of the signaling process from macula densa cells to the glomerular contractile elements has remained unknown. In patch-clamp studies of macula densa cells, we identified an [ NaCl]L-sensitive ATP-permeable large-conductance (380 pS) anion channel. Also, we directly demonstrated the release of ATP (up to $10\>\mu M$) at the basolateral membrane of macula densa cells, in a manner dependent on [ NaCl]L, by using an ATP bioassay technique. Furthermore, we found that glomerular mesangial cells respond with elevations in cytosolic Ca2+ concentration to extracellular application of ATP $(EC_{50}\>0.8\>\mu M)$. Importantly, we also found increases in cytosolic Ca2+ concentration with elevations in [ NaCl]L, when fura-2-loaded mesangial cells were placed close to the basolateral membrane of macula densa cells. Thus, cell-to-cell communication between macula densa cells and mesangial cells, which express P2Y2 receptors, involves the release of ATP from macula densa cells via maxi anion channels at the basolateral membrane. This mechanism may represent a new paradigm in cell-to-cell signal transduction mediated by ATP.

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