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Macula densa cell signaling involves ATP release through a maxi anion channel.
Phillip Darwin Bell1, Jean-Yves Lapointe, Ravshan Sabirov
1Department of Cell Physiology, National Institute for Physiological Sciences, and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Okazaki 444-8585, Japan.
Summary
Macula densa cells release ATP in response to salt levels, signaling to mesangial cells. This ATP release occurs via a specific channel, influencing kidney function and body fluid regulation.
Area of Science:
- Nephrology
- Cell Biology
- Physiology
Background:
- Macula densa cells act as renal biosensors, detecting luminal NaCl concentration.
- They are crucial for regulating salt/water excretion and glomerular hemodynamics.
- The signaling mechanism from macula densa cells to glomerular contractile elements was previously unknown.
Purpose of the Study:
- To elucidate the signaling process between macula densa cells and glomerular mesangial cells.
- To identify the specific molecules and channels involved in this communication.
- To understand the role of this pathway in renal function.
Main Methods:
- Patch-clamp studies on macula densa cells to identify ion channels.
- ATP bioassay to quantify ATP release from macula densa cells.
- Measurement of cytosolic Ca(2+) concentration in mesangial cells using fura-2.
Main Results:
- An NaCl-sensitive, ATP-permeable large-conductance anion channel was identified in macula densa cells.
- ATP release from the basolateral membrane of macula densa cells was demonstrated, dependent on NaCl concentration.
- Glomerular mesangial cells showed increased cytosolic Ca(2+) in response to basolateral ATP release from macula densa cells.
Conclusions:
- Cell-to-cell communication involves ATP release from macula densa cells via maxi anion channels.
- This ATP acts on mesangial cells (expressing P2Y(2) receptors), increasing intracellular calcium.
- This pathway represents a novel mechanism for ATP-mediated cell-to-cell signal transduction in the kidney.