AJP - Renal Physiology, Vol 259, Issue 6 950-F960, Copyright © 1990 by American Physiological Society
Dihydropyridine-sensitive cell volume regulation in proximal tubule: the calcium window
N. A. McCarty and R. G. O'Neil
Department of Physiology, University of Texas Medical School, Houston 77225.
The mechanism underlying the activation of hypotonic cell volume regulation
was studied in rabbit proximal straight tubule (PST). When isolated
non-perfused tubules were exposed to hypotonic solution, cells swelled
rapidly and then underwent a regulatory volume decrease (RVD). The extent
of regulation after swelling was highly dependent on extracellular Ca
concentration ([Ca2+]o), with a half-maximal inhibition (K1/2) for [Ca2+]o
of approximately 100 microM. RVD was blocked by the Ca-channel blockers
verapamil, lanthanum, and the dihydropyridines (DHP) nifedipine and
nitrendipine, implicating voltage-activated Ca channels in the RVD
response. Using the fura-2 fluorescence-ratio technique, we observed that
cell swelling caused a sustained rise in intracellular Ca ([Ca2+]i) only
when [Ca2+]o was normal (1 mM) but not when [Ca2+]o was low (1-10 microM).
Furthermore, external Ca was required early on during swelling to induce
RVD. If RVD was initially blocked by reducing [Ca2+]o or by addition of
verapamil during hypotonic swelling, volume regulation could only be
restored by subsequently inducing Ca entry within the first 1 min or less
of exposure to hypotonic solution. These data indicate a "calcium window"
of less than 1 min, during which RVD is sensitive to Ca, and that part of
the Ca-dependent mechanism responsible for achieving RVD undergoes
inactivation after swelling. It is concluded that RVD in rabbit PST is
modulated by Ca via a DHP-sensitive mechanism in a time-dependent manner.
