RyR1/SERCA1 cross-talk regulation of calcium transport in heavy sarcoplasmic reticulum vesicles

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Date
2003-03-31
Authors
Gilchrist, JSC
Palahniuk, C
Abrenica, B
Rampersad, P
Mutawe, M
Cook, T
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Abstract
We investigated the functional interdependence of sarco-endoplasmic reticulum Ca2+ ATPase isoform 1 and ryanodine receptor isoform 1 in heavy sarcoplasmic reticulum membranes by synchronous fluorescence determination of extravesicular Ca2+ transients and catalytic activity. Under conditions of dynamic Ca2+ exchange ATPase catalytic activity was well coordinated to ryanodine receptor activation/inactivation states. Ryanodine-induced activation of Ca2+ release channel leaks also produced marked ATPase activation in the absence of measurable increases in bulk free extravesicular Ca2+. This suggested that Ca2+ pumps are highly sensitive to Ca2+ release channel leak status and potently buffer Ca2+ ions exiting cytoplasmic openings of ryanodine receptors. Conversely, ryanodine receptor activation was dependent on Ca2+-ATPase pump activity. Ryanodine receptor activation by cytosolic Ca2+ was (i) inversely proportional to luminal Ca2+ load and (ii) dependent upon the rate of presentation of cytosolic Ca2+. Progressive Ca2+ filling coincided with progressive loss of Ca2+ sequestration rates and at a threshold loading, ryanodine-induced Ca2+ release produced small transient reversals of catalytic activity. These data indicate that attainment of threshold luminal Ca2+ loads coordinates sensitization of Ca2+ release channels with autogenic inhibition of Ca2+ pumping. This suggests that Ca2+-dependent control of Ca2+ release in intact heavy sarcoplasmic reticulum membranes involves a Ca2+-mediated "cross-talk" between sarco-endoplasmic reticulum Ca2+ ATPase isoform 1 and ryanodine receptor isoform 1.
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Keywords
Ca2+, RyR, SERCA, cell nucleus, FK506, thapsigargin, ryanodine, INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR, RYANODINE RECEPTOR, CA2+ CHANNELS, SARCOPLASMIC-RETICULUM, ENDOPLASMIC-RETICULUM, NUCLEAR CA2+, FK506-BINDING PROTEIN, SKELETAL-MUSCLE, RELEASE CHANNEL, CYTOSOLIC CA2+
Citation
0008-4212; CAN J PHYSIOL PHARMACOL, MAR 2003, vol. 81, no. 3, p.301 to 310.