A role for Ca(v)1.3 in rat intestinal calcium absorption.
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.
Morgan
E L
EL
Department of Biology (Area 3), University of York, York YO10 5YW, UK.
Mace
O J
OJ
Helliwell
P A
PA
Affleck
J
J
Kellett
G L
GL
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000042:Absorption; D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics*; D015220:Calcium Channels; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D046508:Culture Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007583:Jejunum / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010695:Phlorhizin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; C093712:Cacna1d protein, rat; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D010695:Phlorhizin; D008274:Magnesium; D009543:Nifedipine; D002118:Calcium