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Procaine effects on single sarcoplasmic reticulum Ca2+ release channels
1Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77555.
Biophysical Journal
|April 1, 1993
Summary
Procaine, a calcium release blocker, interacts with closed sarcoplasmic reticulum channels, not open ones. This finding clarifies its mechanism by identifying a specific long-lived closed state involved in channel gating.
Area of Science:
- Biophysics
- Molecular Biology
- Pharmacology
Background:
- Sarcoplasmic reticulum Ca2+ release channels are crucial for muscle contraction.
- Understanding the gating mechanisms of these channels is essential for cellular physiology.
- Procaine is known to affect Ca2+ release, but its precise interaction with the channel was unclear.
Purpose of the Study:
- To investigate the effects of procaine on individual sarcoplasmic reticulum Ca2+ release channels.
- To determine the specific state of the channel (open or closed) that procaine interacts with.
- To refine existing models of channel gating.
Main Methods:
- Single channel recordings in planar lipid bilayers.
- Analysis of channel conductance and open/closed times.
- Computer simulations using a modified gating scheme.
Main Results:
- Procaine did not alter single channel conductance or mean open times.
- Procaine significantly increased the longest closed times of the channel.
- Simulations indicated procaine preferentially binds to a long-lived, Ca(2+)-bound closed state.
Conclusions:
- Procaine selectively interacts with a closed state of the sarcoplasmic reticulum Ca2+ release channel.
- A modified gating model including a long-lived closed state accurately describes channel behavior.
- This interaction may explain previously observed "gearshift" gating phenomena.