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Biophys J. 1993 Oct;65(4):1678-83.

Using large organic cations to probe the nature of ryanodine modification in the sheep cardiac sarcoplasmic reticulum calcium release channel.

Author information

1
Department of Cardiac Medicine, National Heart and Lung Institute, University of London, England.

Abstract

We have reported that the large impermeant organic cations tetrabutyl ammonium (TBA+), tetrapentyl ammonium, and the charged local anesthetic QX314 produce unique reduced conductance states in the purified sheep cardiac sarcoplasmic reticulum Ca2+ release channel when present at the cytoplasmic face of the channel. We have interpreted this as a form of partial occlusion by the blocking cation in wide vestibules of the conduction pathway. Following modification with ryanodine, which causes the channel to enter a reduced conductance state with long open dwell time, these cations block the receptor channel to a level that is indistinguishable from the closed state. The voltage dependence of TBA+'s interaction with the Ca2+ release channel is the same before and after ryanodine modification. The concentration dependence is different, in that the ryanodine-modified channel has one-third the affinity for TBA+, which is accounted for predominantly by changes in the TBA+ on rate. The data are compatible with a structural change in the vestibule of the conduction pathway consequent upon ryanodine binding that reduces the capture radius for blocking ion entry.

PMID:
8274655
PMCID:
PMC1225894
DOI:
10.1016/S0006-3495(93)81201-3
[Indexed for MEDLINE]
Free PMC Article

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