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Morgan, EL, Mace, OJ, Helliwell, PA, Affleck, J and Kellett, GL (2003) A role for Ca(v)1.3 in rat intestinal calcium absorption. Biochem. Biophys. Res. Commun. 312:487-93
Active Ca(2+) absorption through epithelial Ca(2+) channels TRPV5/6 in duodenum is activated by hyperpolarisation. However, when diet and Ca(2+) 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)1.3 alpha(1) protein in apical membrane from proximal jejunum to mid ileum. Perfusion studies in vivo with 1.25 mM luminal Ca(2+) revealed L-type channel activity. Inhibition of glucose absorption with phloridzin strongly inhibited 45Ca(2+) absorption; absorption was inhibited by nifedipine and Mg(2+) and activated by Bay K 8644, none of which affect TRPV5/6. At 10mM Ca(2+), nifedipine inhibited 45Ca(2+) absorption with a time course similar to that at 1.25 mM Ca(2+): 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 Ca(2+) absorption into the body.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology; Absorption; Animals; Calcium/pharmacokinetics; Calcium Channels; Calcium Channels, L-Type/drug effects; Calcium Channels, L-Type/metabolism; Culture Techniques; Intestinal Mucosa/metabolism; Intestines/metabolism; Ion Channel Gating/drug effects; Ion Channel Gating/physiology; Jejunum/metabolism; Magnesium/pharmacology; Male; Nifedipine/pharmacology; Phlorhizin/pharmacology; Rats; Rats, Wistar