Alternative perspective on intestinal calcium absorption: proposed complementary actions of Ca(v)1.3 and TRPV6

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.