Identification and localization of calcium channel α1 and β subunit isoforms in the kidney

Abstract

The distal nephron of the kidney plays a key role in the regulation of renal calcium excretion. Although calcium filtered at the glomerulus is reabsorbed along the whole length of the nephron, active, and by inference transcellular, transport has been demonstrated primarily in the micropuncture distal tubule [1, 2], and more specifically the distal convoluted tubule (DCT) [3] and connecting tubule (CNT) [4]. Active transport has also been observed under certain conditions in the cortical thick ascending limb (CTAL) [4, 5], although this is controversial [6]. Furthermore, the action of parathyroid hormone (PTH) to enhance calcium reabsorption in the CNT [3] and CTAL [5] is responsible for its hypocalciuric effect. The mechanism and regulation of calcium reabsorption at the cellular level have recently been reviewed [7]. Figure 1 illustrates a model of transcellular calcium transport in a distal tubule epithelial cell, based on current knowledge. Cytosolic calcium is actively extruded at the basolateral membrane by a calcium pump or sodium-calcium exchanger [8, 9]. Until recently, however, little was known about how calcium entered these cells at the apical surface, except that it must pass down a steep concentration gradient, from millimolar concentrations in the tubular fluid [1] to submicromolar concentrations within the cytosol [10], and also down a transmembrane electrical gradient of between -35 mV and -87 mV [11, 12], suggesting a passive transport mechanism.