Cav1.3 does not contribute to active 1,25D‐regulated intestinal Ca absorption

Abstract

Intestinal Ca absorption occurs through a 1,25(OH)2D3 (1,25D)‐regulated transcellular pathway when habitual dietary Ca intake is low. Recently the L‐type Ca channel, Cav1.3, has been proposed to mediate active Ca absorption. We examined the role of Cav1.3 in Ca absorption using mouse models. Study 1 examined the relationship between Cav1.3 mRNA level and Ca absorption in a genetically diverse population of mice fed a normal (0.5%) or low (0.25%) Ca diet from 3–12 wks of age. Ca absorption was measured by oral gavage of a buffer containing 10 mM fructose and Ca45. Low Ca diets induced an increase in 1,25D and Ca absorption. Cav1.3 mRNA was detected in the duodenum, however, it was not associated with Ca absorption (r=−0.09, p=0.3) nor was it increased by low Ca intake (p=0.4). Study 2 examined whether glucose‐induced depolarization of the apical membrane of enterocytes enhances Ca absorption through Cav1.3. 10 wk‐old mice were fed high (1%) or low (0.125%) Ca diets for 1 wk. Ca absorption was examined using transport buffers containing Ca45 and either 25 mM glucose or fructose. While low Ca intake doubled Ca absorption, the sugar in the transport buffer did not increase Ca absorption efficiency (p=0.6) regardless of diet (p=0.19). Our data provide no support for the hypothesis that Cav1.3 and glucose‐induced depolarization are critical components of Ca absorption physiology.Grant Funding Source: NIH awards DK54111 and ES019103 (JCF)