Calcium and polyamine regulated calcium-sensing receptors in cardiac tissues.
Activation of a calcium-sensing receptor (Ca-SR) leads to increased intracellular calcium concentration and altered cellular activities. The expression of Ca-SR has been identified in both nonexcitable and excitable cells, including neurons and smooth muscle cells. Whether Ca-SR was expressed and functioning in cardiac myocytes remained unclear. In the present study, the transcripts of Ca-SR were identified in rat heart tissues using RT-PCR that was further confirmed by sequence analysis. Ca-SR proteins were detected in rat ventricular and atrial tissues as well as in isolated cardiac myocytes. Anti-(Ca-SR) Ig did not detect any specific bands after preadsorption with standard Ca-SR antigens. An immunohistochemistry study revealed the presence of Ca-SR in rat cardiac as well as other tissues. An increase in extracellular calcium or gadolinium induced a concentration-dependent sustained increase in [Ca2+]i in isolated ventricular myocytes from adult rats. Spermine (1-10 mm) also increased [Ca2+]i. Pre-treatment of cardiac myocytes with thapsigargin or U73122 abolished the extracellular calcium, gadolinium or spermine-induced increase in [Ca2+]i. The blockade of Na+/Ca2+ exchanger or voltage-dependent calcium channels did not alter the extracellular calcium-induced increase in [Ca2+]i. Finally, extracellular calcium, gadolinium and spermine all increased intracellular inositol 1,4,5-triphosphate (IP3) levels. Our results demonstrated that Ca-SR was expressed in cardiac tissue and cardiomyocytes and its function was regulated by extracellular calcium and spermine.
Wang
Rui
R
Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada. wangrui@duke.usask.ca
Xu
Changqing
C
Zhao
Weimin
W
Zhang
Jing
J
Cao
Kun
K
Yang
Baofeng
B
Wu
Lingyun
L
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D003001:Cloning, Molecular; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008099:Liver / Q000502:physiology; D008297:Male; D009928:Organ Specificity; D011073:Polyamines / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics*; D011994:Recombinant Proteins / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D011073:Polyamines; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C473605:extracellular calcium cation-sensing receptor, rat; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium