Macula densa cell signaling involves ATP release through a maxi anion channel.
Macula densa cells are unique renal biosensor cells that detect changes in luminal NaCl concentration ([NaCl](L)) and transmit signals to the mesangial cellafferent 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 microM) 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 Ca(2+) concentration to extracellular application of ATP (EC(50) 0.8 microM). Importantly, we also found increases in cytosolic Ca(2+) 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 P2Y(2) 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.
Bell
Phillip Darwin
PD
Department 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.
Lapointe
Jean-Yves
JY
Sabirov
Ravshan
R
Hayashi
Seiji
S
Peti-Peterdi
Janos
J
Manabe
Ken-Ichi
K
Kovacs
Gergely
G
Okada
Yasunobu
Y
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D005920:Glomerular Mesangium / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D009130:Muscle, Smooth / Q000502:physiology; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D010673:Pheochromocytoma; D011817:Rabbits; D051381:Rats; D012965:Sodium Chloride / Q000494:pharmacology
D007473:Ion Channels; D012965:Sodium Chloride; D000255:Adenosine Triphosphate