A role for Cav1.3 in rat intestinal calcium absorption

Active Ca2+ absorption through epithelial Ca2+ channels TRPV5/6 in duodenum is activated by hyperpolarisation. However, when diet and Ca2+ are plentiful, digestion products cause depolarisation. We therefore used homology-based PCR from a rat jejunal mucosal cDNA preparation to reveal the presence of the neuroendocrine L-type isoform Ca(v)1.3alpha(1). Immunocytochemical labelling and immunoblotting localised Ca(v)1.3alpha(1) protein in apical membrane from proximal jejunum to mid ileum. Perfusion studies in vivo with 1.25 mM luminal Ca2+ revealed L-type channel activity. Inhibition of glucose absorption with phloridzin strongly inhibited Ca-45(2+) absorption; absorption was inhibited by nifedipine and Mg2+ and activated by Bay K 8644, none of which affect TRPV5/6. At 10 mM Ca2+, nifedipine inhibited Ca-45(2+) absorption with a time course similar to that at 1.25 mM Ca2+: absorption was therefore channel-mediated rather than paracellular. We suggest that in times of dietary sufficiency, Ca(v)1.3 may mediate a significant route of Ca2+ absorption into the body. (C) 2003 Elsevier Inc. All rights reserved.