Regulation of ryanodine receptor activity by cytosolic and luminal Ca2+ in the presence of ATP
Barbora Tencerová*, Marta Gaburjáková, Alexandra Zahradníková
Institute of Molecular physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovakia
*barbora.tencerova@savba.sk
It has long been known that the Ca2+ content of the sarcoplasmic reticulum (SR) is a strong stimulator of calcium induced calcium release (CICR) and one of the determinants of excitation-contraction coupling (EC coupling) gain. Ryanodine receptor (RyR2) is a Ca2+ activated, Ca2+ permeable channel of the sarcoplasmic reticulum (SR) that mediates CICR in the cardiac muscle cells. There is growing evidence that free [Ca2+] in the lumen of the SR regulates the excitability of Ca2+ release by stimulating the RyR2 channels.
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Fig. 1.
The effect of Ca2+
on the response of RyR2 to ATP. The potency of ATP as RyR2 channel activator significantly increased
with the presence of luminal Ca2+.
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Fig. 2. The effect
of luminal Ca2+ on the kinetics of RyR2. Statistically significant
differences are shown for interval corresponding to Pmax
in the absence of luminal Ca2+, indicating that luminal Ca2+
modifies the gating kinetics of RYR2. |
Our results present the effect of luminal Ca2+ on RyR2 in the presence of ATP, because it has been shown that ATP is an important physiological coagonist.
We found that elevation of the luminal Ca2+
concentration enhanced both, the potency (EC50) and the efficacy (Pmax) of ATP as activator of the RyR2 channel.
The effect on EC50 was already saturated at 1 mM luminal Ca2+
(Fig. 1). In the absence of luminal Ca2+ the average dwell times
were significantly shortened and the frequency of openings was significantly
increased in comparison to experiments performed in the presence of luminal Ca2+
(Fig. 2). The changes of PO by ATP in the presence of 1 mM luminal
Ca2+, as well as the changes of