A role for Ca(v)1.3 in rat intestinal calcium absorption

Area of Science:

• Physiology
• Molecular Biology
• Gastroenterology

Background:

• Epithelial calcium (Ca2+) absorption is primarily mediated by TRPV5/6 channels in the duodenum, activated by hyperpolarization.
• Dietary sufficiency and digestion can lead to depolarization, suggesting alternative calcium absorption pathways.

Purpose of the Study:

• To investigate the presence and function of L-type calcium channels in intestinal calcium absorption.
• To determine if Ca(v)1.3 channels contribute to calcium uptake in the jejunum and ileum.

Main Methods:

• Homology-based PCR was used to identify Ca(v)1.3alpha(1) in rat jejunal cDNA.
• Immunocytochemistry and immunoblotting localized Ca(v)1.3 alpha(1) protein.
• In vivo perfusion studies with varying calcium concentrations and channel inhibitors were performed.

Main Results:

• Ca(v)1.3 alpha(1) protein was found in the apical membrane of the proximal jejunum to mid ileum.
• L-type channel activity was observed during in vivo perfusion.
• 45Ca(2+) absorption was inhibited by phloridzin, nifedipine, and Mg(2+), and activated by Bay K 8644, indicating Ca(v)1.3 channel involvement.
• Nifedipine's effect on 45Ca(2+) absorption was time-dependent and concentration-independent, suggesting channel-mediated, not paracellular, absorption.

Conclusions:

• The neuroendocrine L-type isoform Ca(v)1.3alpha(1) is present and functional in the rat small intestine.
• Ca(v)1.3 channels mediate a significant pathway for intestinal calcium absorption, particularly under conditions of dietary sufficiency.
• This finding expands our understanding of calcium homeostasis beyond TRPV5/6 channels.