Alternative perspective on intestinal calcium absorption: proposed complementary actions of Cav1.3 and TRPV6

Abstract

Transcellular models of dietary Ca(2+) absorption by the intestine assign essential roles to TRPV6 and calbindin-D(9K) . However, studies with gene-knockout mice challenge this view. Something fundamental is missing. The L-type channel Ca(v) 1.3 is located in the apical membrane from the duodenum to the ileum. In perfused rat jejunum in vivo and in Caco-2 cells, Ca(v) 1.3 mediates sodium glucose transporter 1 (SGLT1)-dependent and prolactin-induced active, transcellular Ca(2+) absorption, respectively. TRPV6 is activated by hyperpolarization and is vitamin D dependent; in contrast, Ca(v) 1.3 is activated by depolarization and is independent of calbindin-D(9K) and vitamin D. This review considers evidence supporting the idea that Ca(v) 1.3 and TRPV6 have complementary roles in the regulation of intestinal Ca(2+) absorption as depolarization and repolarization of the apical membrane occur during and between digestive periods, respectively, and as chyme moves from one intestinal segment to another and food transit times increase. Reassessment of current arguments for paracellular flow reveals that key phenomena have alternative explanations within the integrated Ca(v) 1.3/TRPV6 view of transcellular Ca(2+) absorption.

Hepcidin and 1,25(OH)2D3effectively restore Ca2+transport in β-thalassemic mice: reciprocal phenomenon of Fe2+and Ca2+absorption

“…The duodenal transcellular calcium transport was actually very complex and exhibited highly redundant cellular mechanisms. Although TRPV5, TRPV6, and L-type calcium channel (e.g., Ca v 1.3) have been reported to be present in the apical membrane of the duodenal enterocytes (17,21), it was likely that only the L-type calcium channel contributed predominantly to the apical uptake in 1,25(OH) 2 D 3 -treated BKO mice.…”

Acute interactions between intestinal sugar and calcium transport in vitro

“…The L-type Ca 2ϩ channel Ca(v)1.3 has been proposed to mediate active intestinal Ca 2ϩ transport in combination with TRPV6 (20,46), particularly because active Ca 2ϩ transport is normal in TRPV6 Ϫ/Ϫ mice (5). However, expression of Ca(v)1.3 in enterocytes is ϳ20-to 30-fold less than TRPV6 (data not shown), and Ca(v)1.3 levels did not significantly respond to a low-Ca 2ϩ diet (Fig.…”

Pre-suckling calcium supplementation effectively prevents lactation-induced osteopenia in rats

“…Since the SGLT1-induced activation of Ca v 1.3 was essential for the suckling-and PRL-induced calcium absorption (3,19,25), SGLT1 substrates (i.e., glucose and/or galactose) were added in the formula to potentiate calcium absorptive capacity. Both monosaccharides did not increase the body weight of lactating rats (data not shown).…”