CHARACTERIZATION OF CA2-RELEASE CHANNELS IN FETAL AND ADULT-RAT HEARTS()

The goal of this study was to characterize the Ca2+-release channel in whole homogenates of left (LV) and right ventricles (RV) of fetal (22 days in gestation) and adult Sprague-Dawley rat hearts using [H-3]rya nodine binding and Ca-45(2+) fluxes. Although many features of the Ca2 +-release channels were similar in fetal and adult hearts, biochemical assays revealed quantitative differences. Similar properties include 1) Ca2+-sensitive cooperative ryanodine binding to Ca2+-release channe l, measured as Ca2+ concentration for half-maximal activation (fetal L V: 0.13 +/- 0.02 mu M; adult LV: 0.15 +/- 0.02 mu M) and Hill coeffici ent (fetal LV: 2.5 +/- 0.9; adult LV: 2.7 +/- 0.5), and 2) caffeine-se nsitive ryanodine binding, measured as the percent increase in ryanodi ne binding induced by caffeine (fetal LV: 148.8 +/- 16.9% vs. adult LV : 171.4 +/- 34.9%). The distinguishing property was the lower Ca2+-rel ease channel density in the fetal heart (LV: 0.22 +/- 0.03 pmol/mg pro tein) compared with adult heart (LV: 0.59 +/- 0.04 pmol/mg protein; P < 0.05), as determined by [H-3]ryanodine binding. The lower density of Ca2+-release channel is supported by the finding that there is very l ow ryanodine-sensitive oxalate-supported Ca-45(2+) uptake in the fetal heart. The tested characteristics of the Ca2+-release channel were si milar between LV and RV in both fetal and adult rat hearts. Our result s indicate that expression of Ca2+-release channels in sarcoplasmic re ticulum increases during postnatal growth in the rat heart. This is co nsistent with previous physiological reports that Ca2+ available for e xcitation-contraction coupling in the fetal heart is derived mainly fr om transsarcolemmal Ca2+ influx.