Table of Contents
ISRN Physiology
Volume 2013, Article ID 309074, 6 pages
http://dx.doi.org/10.1155/2013/309074
Research Article

Acute Activation of the Renal Betaine/GABA Transporter in Response to a Decrease in Extracellular Calcium

Department of Cellular & Integrative Physiology, Indiana University School of Medicine, MS-385, 635 Barnhill Drive, Indianapolis, IN 46223, USA

Received 24 August 2012; Accepted 18 September 2012

Academic Editors: G.-R. Li and A. Peres

Copyright © 2013 Nehal R. Parikh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The betaine/GABA transporter (BGT1) is important for osmoprotection in kidney medullary cells. We previously reported an acute (30 min) increase in extracellular Ca2+ caused dose dependent inhibition of BGT-1 in renal MDCK cells. To determine if extracellular Ca2+ might be a local regulator of BGT-1, we have tested the response to low Ca2+ serum-free growth medium (LCM, 0.05 mM Ca2+). Chronic treatment (8–24 h) of MDCK cell monolayers completely blocked hypertonic adaptation of BGT1 and disrupted tight junctions. In contrast, acute treatment activated BGT1 transport within 30 min in MDCK cells previously adapted to hypertonic growth medium containing normal Ca2+ (1.6 mM). Activation was significant after 60–90 min and was independent of medium osmolarity. Peak transport was increased 50% in isotonic LCM and 100% in hypertonic (500 mOsm) LCM over controls. The activation was reversed by restoration of normal Ca2+. Perfusion of Fura-2-loaded MDCK cells with LCM decreased intracellular Ca2+ by 31% within 6-7 min. Inclusion of staurosporine (0.6 μM), a protein kinase C inhibitor, potentiated the action of LCM. We suggest that activation of BGT1 by LCM may be due in part to inhibition of protein kinase C.