Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adrenergic beta-Agonists / pharmacology
-
Animals
-
Caffeine / pharmacology
-
Calcium / analysis
-
Calcium / metabolism*
-
Calcium-Transporting ATPases / biosynthesis
-
Calcium-Transporting ATPases / drug effects
-
Cells, Cultured
-
Central Nervous System Stimulants / pharmacology
-
Electric Stimulation
-
Homeostasis / physiology
-
Hypoxia / metabolism*
-
Intracellular Fluid / chemistry
-
Intracellular Fluid / drug effects
-
Isoproterenol / pharmacology
-
Male
-
Myocytes, Cardiac / drug effects
-
Myocytes, Cardiac / metabolism*
-
Rats
-
Rats, Sprague-Dawley
-
Ryanodine Receptor Calcium Release Channel / biosynthesis
-
Ryanodine Receptor Calcium Release Channel / drug effects
-
Sarcoplasmic Reticulum / metabolism
-
Sarcoplasmic Reticulum Calcium-Transporting ATPases
-
Sodium-Calcium Exchanger / metabolism
-
Spectrometry, Fluorescence
-
Time Factors
Substances
-
Adrenergic beta-Agonists
-
Central Nervous System Stimulants
-
Ryanodine Receptor Calcium Release Channel
-
Sodium-Calcium Exchanger
-
Caffeine
-
Sarcoplasmic Reticulum Calcium-Transporting ATPases
-
Calcium-Transporting ATPases
-
Isoproterenol
-
Calcium