Angiotensin II increases the intracellular calcium activity in podocytes of the intact glomerulus.
Angiotensin II increases the intracellular calcium activity in podocytes of the intact glomerulus.


BACKGROUND
Knowledge about biological functions of podocytes in the glomerulus is limited because of its unique anatomical location. Here we introduce a new method for measuring the intracellular calcium activity ([Ca2+]i) in the podocyte in the intact glomerulus.


METHODS
With the help of fluorescence high-resolution digital imaging and a recently developed ultraviolet laser-scanning microscope, [Ca2+]i was measured in fura-2-loaded glomeruli and single podocytes of intact microdissected rat glomeruli.


RESULTS
Angiotensin II (Ang II) increased [Ca2+]i reversibly in a biphasic and concentration-dependent manner. In contrast to Ang II, bradykinin, thrombin, arginine vasopressin, and serotonin did not change [Ca2+]i in the glomerulus. At reduced extracellular Ca2+ activity, Ang II released [Ca2+]i from intracellular stores, but the second phase, corresponding to a Ca2+ influx from the extracellular space, was absent. The L-type Ca2+ channel blocker nicardipine did not influence the Ang II-mediated [Ca2+]i increase, and an increase of the extracellular K+ concentration did not change [Ca2+]i in the glomerulus. The angrotensin II type I (AT1) receptor antagonist losartan inhibited the Ang II-mediated [Ca2+]i increase. Confocal [Ca2+]i measurements using fura-2 or fluo-3 or fluo-4 on the single cell level show that some of the Ang II-mediated [Ca2+]i response originated from podocytes. Costaining with calcein allowed the identification of podocytes because of the characteristic morphology and location in relationship to the capillary network.


CONCLUSIONS
These data suggest that podocytes in the intact glomerulus respond to Ang II with an increase of [Ca2+]i via an AT1 receptor.
Nitschke
R
R
Division of Nephrology, Department of Medicine, and Physiologisches Institut, Albert-Ludwigs-Universität, Freiburg, Germany.
Henger
A
A
Ricken
S
S
Gloy
J
J
Müller
V
V
Greger
R
R
Pavenstädt
H
H
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005456:Fluorescent Dyes; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D005456:Fluorescent Dyes; D000804:Angiotensin II; D001127:Arginine Vasopressin; D012701:Serotonin; D013917:Thrombin; D001920:Bradykinin; D002118:Calcium