A mechanism of Ca2+ release from Ca2+ stores coupling to the Na+/Ca2+ exchanger in cultured smooth muscle cells.
We previously observed Ca2+ release from intracellular Ca2+ stores caused by reduction in extracellular Na+ concentration ([Na+]o). The purpose of this study was to determine whether lowering [Na+]o can elicit Ca2+ release from Ca2+ stores via the Na+/Ca2+ exchanger and to elucidate the mechanisms related to the Ca2+ release pathway in cultured longitudinal smooth muscle cells obtained from guinea pig ileum. Low [Na+]o-induced Ca2+ release was inhibited by antisense oligodeoxynucleotides for Na+/Ca2+ exchanger type 1 (anti-NCX). Application of anti-NCX to cells attenuated both the number of Ca2+ responding cells and the expression of the exchanger. Moreover, microinjection of heparin, a blocker of inositol 1,4,5-trisphosphate (IP3) receptors, into the cells inhibited low [Na+]o-induced Ca2+ release. These findings suggest that low [Na+]o-induced Ca2+ release occurs through an IP3-induced Ca2+ release mechanism due to changes in the Ca2+ flux regulated by the Na+/Ca2+ exchanger.
Hisamitsu
T
T
Department of Pharmacology, School of Pharmaceutical Science, Showa University, Shinagawa, Tokyo, Japan. hisamits@pharm.showa-u.ac.jp
Ohata
H
H
Kawanishi
T
T
Iwamoto
T
T
Shigekawa
M
M
Amano
H
H
Yamada
S
S
Momose
K
K
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D002794:Choline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016257:Fura-2 / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D006168:Guinea Pigs; D006493:Heparin / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D007082:Ileum; D015151:Immunoblotting; D008297:Male; D008845:Microinjections; D009130:Muscle, Smooth / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D005971:Glutamates; D016376:Oligonucleotides, Antisense; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; C014574:gamma-glutamylmethylamide; D001285:Atropine; D006632:Histamine; D002217:Carbachol; D006493:Heparin; D002794:Choline; D002118:Calcium; D016257:Fura-2