Dihydropyridine-sensitive cell volume regulation in proximal tubule: the calcium window

• Published in: The American journal of physiology Vol. 259; no. 6 Pt 2; pp. F950 - F960
• Main Authors: McCarty, N A, O'Neil, R G
• Format: Journal Article
• Language: English
• Published: United States 01-12-1990
• Subjects: Animals; Calcium - metabolism; Calcium - physiology; Calcium Channel Blockers - pharmacology; Dihydropyridines - pharmacology; Female; In Vitro Techniques; Intracellular Membranes - metabolism; Kidney Tubules - cytology; Kidney Tubules - drug effects; Kidney Tubules - metabolism; Lanthanum - pharmacology; Rabbits; Time Factors
• ISSN: 0002-9513
• DOI: 10.1152/ajprenal.1990.259.6.f950

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.