Membrane repolarization stops caffeine-induced Ca2+ release in skeletal muscle cells

Area of Science:

• Muscle physiology
• Cellular electrophysiology
• Calcium signaling

Background:

• The precise control of calcium release in skeletal muscle is crucial for excitation-contraction coupling.
• The role of membrane potential in regulating calcium release channels, particularly the ryanodine receptor, remains an area of active investigation.

Purpose of the Study:

• To investigate the influence of membrane potential on the Ca(2+)-induced Ca(2+)-release channel in rat skeletal myoballs.
• To determine if repolarization can inhibit calcium release mediated by these channels.

Main Methods:

• Combined patch-clamp electrophysiology with fura-2 calcium measurements in rat skeletal myoballs.
• Utilized caffeine application to induce calcium release and manipulated membrane potential (depolarization and repolarization).

Main Results:

• Discovered a phenomenon termed RISC (repolarization-induced stop of Ca2+ release), where membrane repolarization actively closes caffeine-activated calcium release channels.
• Demonstrated that RISC is voltage- and time-dependent, requiring prior membrane depolarization to activate the release channels.
• Provided evidence that the ryanodine receptor functions as the physiological depolarization-induced calcium-release channel.

Conclusions:

• Skeletal muscle calcium release channels exhibit bidirectional voltage control, being activated by depolarization and inhibited by repolarization.
• The findings support the model of a voltage sensor in the transverse tubule membrane controlling the sarcoplasmic reticulum's calcium release channel.
• This bidirectional control mechanism offers new insights into the regulation of muscle contraction.