Calcium homeostasis in rat cardiomyocytes during chronic hypoxia: a time course study.
The present study determined Ca2+ handling in the hearts of rats subjected to chronic hypoxia (CH). Spectrofluorometry was used to measure intracellular Ca2+ concentration ([Ca2+]i) and its responses to electrical stimulation, caffeine, and isoproterenol in myocytes from the right ventricle of rats breathing 10% oxygen for 1, 3, 7, 14, 21, 28, and 56 days and age-matched controls. The protein expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and its ryanodine receptor (RyR) were measured. The uptake of 45Ca2+ by SERCA, release by RyR, and extrusion by Na+/Ca2+ exchange (NCX) were determined. It was found that Ca2+ homeostasis and Ca2+ responses to beta-adrenoceptor stimulation reached a new equilibrium after 4 wk of CH. Ca2+ content in the sarcoplasmic reticulum (SR) was reduced, but cytosolic Ca2+ remained unchanged after CH. Expression of SERCA and its Ca2+ uptake, Ca2+ release via RyR, and NCX activity were suppressed by CH. The results indicate impaired Ca2+ handling, which may be responsible for the attenuated Ca2+ responses to beta-adrenoceptor stimulation in CH.
Dept. of Physiology, Faculty of Medicine, Univ. of Hong Kong, 21 Sassoon Rd., Hong Kong, China. wongtakm@hkucc.hku.hk
Jian-Ming
JM
Pei
Gennadi M
GM
Kravtsov
Song
S
Wu
Rapti
R
Das
Man Lung
ML
Fung
Tak Ming
TM
Wong
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis / Q000187:drug effects; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004558:Electric Stimulation; D006706:Homeostasis / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism*; D007424:Intracellular Fluid / Q000737:chemistry / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000096:biosynthesis / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D000697:Central Nervous System Stimulants; D019837:Ryanodine Receptor Calcium Release Channel; D019831:Sodium-Calcium Exchanger; D002110:Caffeine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D007545:Isoproterenol; D002118:Calcium