
Calcium Modulation / Regulation
The calcium sensing receptor (CaR) is an understudied component of the group of mechanisms that control circulating calcium levels and are therefore intimately involved in calcium metabolism and homeostasis. Our hypothesis is that the CaR has a role in controlling calcium concentrations and fluctuations in cardiac dysfunction, and might be a compensatory mechanism due to the loss of the more traditional mechanisms of calcium transport in the excitation-contraction pathway. As a model for acute stress, we will employ a burn model that is currently used at UTMB-Galveston to study mechanisms of post-burn bone loss and the involvement of the parathormone-calcitonin pathway. This model has yielded data regarding down-regulation of parathyroid CaR and leads to acute cardiac distress.
Our goal is to understand the role of the CaR in cardiac dysfunction and heart failure associated with severe, acute trauma. Initially we will use the acute stress tissue from the ovine source. We then plan to expand our experimentation as an extension of our studies of mechanisms associated with heart failure and recovery, and examine the involvement of the CaR in chronic heart disease, intestinal dysfunction and burns.
Collaborators:
Dr. Gordon Klein, UTMB-Galveston; Dr. O. H. Frazier, Texas Heart Institute
Calcium sensing receptor
Gordon Klein (UTMB-Pediatric Gastroenterology) Perenlie Enkhbataar (UTMB), Dan Traber (UTMB-Anesthesiology), L. Max Buja, Collette Jonkam (UTMB), Brian Poindexter, Roger Bick, Calcium-sensing receptor (red) shown in the vascular endothelium and adventitial microvasculature of this artery following burn injury. Reference - Klein, GL et al, Burns. 2008 34:320-325.
Small intestine
Brian Poindexter, Gordon Klein, Roger Bick,
Small intestine villi showing distribution,
Small intestine villi showing distribution of the calcium sensing receptor (red). Blue shows nuclei, green shows f-actin.
Small intestine
Roger Bick, Gordon Klein, Brian Poindexter, Small intestine submucosa and muscularis externa showing distribution of the calcium sensing receptor (red). Blue shows nuclei, green shows f-actin.
Auerbach's plexus
Roger Bick, Gordon Klein (UTMB), Brian Poindexter,
Myenteric plexus of small intestine stained for the calcium sensing receptor (red).
Brush border
Brian Poindexter, Rosemary Kozar (UT Surgery), Gordon Klein, Roger Bick, Brush border of small intestine (green-f actin) on enterocytes with blue nuclei and red calcium sensing protein inclusions.
Calcium sensing receptor
Brian Poindexter, Rosemary Kozar (UT Surgery), Gordon Klein, Roger Bick, Calcium sensing receptor (red) in the myenteric nerve plexus of the muscularis externa between 2 layers of smooth muscle.
CaR membrane cutout
Brian Poindexter, Roger Bick,
A model of a deconvoluted stacked-image rendition (32 images) to demonstrate the intimate association of the CaR protein (red) with the FX membrane probe (green). Magnification 1500X. Reference - Klein, GL et al, Burns. 2008 34:320-325.
CaR membrane probe
Brian Poindexter, Roger Bick, Model of a deconvoluted stacked-image rendition (32 images) of multiple cells to demonstrate the intimate association of the CaR protein (red) with the FX membrane probe (green). Magnification 600X.
Calcium sensing receptor
Gordon Klein (UTMB-Pediatric Gastroenterology) Perenlie Enkhbataar (UTMB), Dan Traber (UTMB-Anesthesiology), L. Max Buja, Collette Jonkam (UTMB), Brian Poindexter, Roger Bick. Localization of the Calcium-sensing receptor (red) to the endocardium and sub-intimal layer.
Calcium sensing receptor
Brian Poindexter, Gordon Klein (UTMB-Pediatric Gastroenterology) Perenlie Enkhbataar (UTMB), Dan Traber (UTMB-Anesthesiology), L. Max Buja, Collette Jonkam (UTMB), Roger Bick.
Localization of the Calcium-sensing receptor (red) to the intra-myocardial microvasculature and the adventitia of the heart.
GI muscularis externa
Roger Bick, Brian Poindexter, Red is CaR, green is f-actin, blue shows nuclei. Magnification x400.
Ileum
Brian Poindexter, Rosemary Kozar, Roger Bick,
Red is CaR, green is f-actin, blue shows nuclei. Magnification x400
Smooth muscle
Brain Poindexter, Roger Bick, Smooth muscle cells of the muscularis externa of the GI tract. Magnification x600
Tight junctions
Brain Poindexter, Charles Cox (Pediatric Surgery-UT), Roger Bick, Tight junctions in GI endothelium reveled by the protein claudin (red)
Villi cross-section
Brian Poindexter, Gordon Klein, Rosemary Kozar, Roger Bick, Cross section of GI villi showing CaR protein (red), nuclei (blue) and co-localization of CaR and f-actin (yellow)
Calcium channel proteins
David Sheikh-Hamad et al, 3D reconstruction of stacked images showing perinuclear stanniocalcin-1 in a binucleate cultured adult cardiomyocyte.

