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A proton gradient controls a calcium-release channel in sarcoplasmic reticulum
Summary
A proton gradient across sarcoplasmic reticulum membranes helps keep calcium release channels closed during muscle contraction. Disrupting this gradient causes channels to open, releasing calcium and generating tension.
Area of Science:
- Muscle Physiology
- Cellular Biophysics
- Membrane Transport
Background:
- Sarcoplasmic reticulum vesicles generate proton gradients during calcium uptake.
- These gradients are crucial for regulating calcium release in muscle fibers.
Purpose of the Study:
- To investigate the role of proton gradients in regulating calcium release channels in skeletal muscle.
- To determine the relationship between pH, calcium release, and muscle tension.
Main Methods:
- Using skinned rabbit psoas muscle fibers and isolated sarcoplasmic reticulum vesicles.
- Employing proton ionophores (gramicidin, nigericin, CCP) to dissipate proton gradients.
- Utilizing dicyclohexylcarbodiimide (DCC) to probe protein interactions and ion flow.
Main Results:
- Dissipating the proton gradient induced transient tension in muscle fibers.
- Changes in medium pH also triggered transient tensions, indicating pH sensitivity.
- Physiological calcium levels inhibited pH-induced calcium release, while DCC blocked release without affecting uptake.
Conclusions:
- A proton gradient across the sarcoplasmic reticulum membrane likely maintains calcium release channels in a closed state.
- Dissipation of this gradient or elevated myoplasmic calcium promotes channel opening and calcium release.
- The proteolipids of sarcoplasmic reticulum may be involved in the calcium release channel or its regulation by proton fluxes.