Regulation of the gating of the sheep cardiac sarcoplasmic reticulum ca2+-release channel by luminal Ca2+ |
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Authors: | R Sitsapesan A J Williams |
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Institution: | (1) Department of Cardiac Medicine, National Heart and Lung Institute, SW3 6LY London, UK |
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Abstract: | We investigated the effects of changes in luminal Ca2+] on the gating of native andpurified sheep cardiac sarcoplasmic reticulum (SR) Ca2+-release channels reconstituted intoplanar phospholipid bilayers. The open probability (P
o
)of channels activated solely by cytosolic Ca2+ was greater at positive than negative holding potentials. Channels activatedsolely by 10 m cytosolic Ca2+ exhibited no change in steady-stateP
o
or in the relationship betweenP
o
and voltage when the luminalCa2+] was increased from nanomolar to millimolar concentrations. In the absence of activating concentrationsof cytosolic Ca2+, the channel can be activated by the phosphodiesterase inhibitor sulmazole (AR-L 115BS). However, cytosolicCa2+-independent activation of the channel by sulmazole requires luminal Ca2+. In the presence ofsulmazole, at picomolar luminal Ca2+] the channel remains completely closed. Increasing the luminal Ca2+]to millimolar levels markedly increases the P
o
via an increase in theduration of open events. The P
o
and duration of the sulmazole-activated, luminalCa2+-dependent channel openings are voltage dependent. In the presence of micromolar luminal Ca2+, theP
o
and duration of sulmazole-activated openings are greater atnegative voltages. However, at millimolar luminal Ca2+], long openings are also observed at positive voltages and theP
o
appears to be similar at positive and negative voltages. Our findings indicate thatthe regulation of channel gating by luminal Ca2+ depends on the mechanism of channel activation.We would like to thank Dr Allan Lindsay for the preparation of the purified SR Ca2+-release channels. This work was supported by the British Heart Foundation. |
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Keywords: | Ca2+-release channels Sarcoplasmic reticulum Cardiac Sulmazole |
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