A role for Ca(v)1.3 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_v1.3α₁. Immunocytochemical labelling and immunoblotting localised Ca_v1.3α₁ 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 ⁴⁵Ca²⁺ 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 ⁴⁵Ca²⁺ 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_v1.3 may mediate a significant route of Ca²⁺ absorption into the body.