A proton-led model of fast calcium waves

Area of Science:

• Cell Biology
• Biophysics
• Molecular Cell Biology

Background:

• Fast calcium waves (10-30 microm/s) are observed in eukaryotic cells and cell-free extracts.
• Existing models propose calcium wave propagation via reaction-diffusion cycles involving extracellular diffusion along endoplasmic reticula.
• Endoplasmic reticular calcium release is typically attributed to diffusion along the reticulum's outer surface.

Purpose of the Study:

• To propose a novel tandem wave model for calcium wave propagation.
• To describe a reaction-diffusion cycle occurring within the endoplasmic reticulum lumen.
• To explain the coordinated propagation of luminal and extra-luminal calcium waves.

Main Methods:

• Theoretical modeling of reaction-diffusion cycles within the endoplasmic reticulum lumen.
• Investigation of proton-induced proton release from luminal calsequestrin/calreticulin.
• Analysis of ion flux (calcium and hydrogen) across the reticular membrane.

Main Results:

• Proposed a tandem wave model involving a luminal reaction-diffusion cycle.
• Demonstrated that luminal [H+] increases can trigger proton release from storage proteins.
• Predicted coordinated luminal and extra-luminal waves mediated by ion transport across the reticular membrane.

Conclusions:

• The tandem wave model offers a new mechanism for fast calcium wave propagation.
• The model predicts autorelease of protons and waves of [H+], [Ca2+], and voltage within reticula.
• Luminal waves may propagate independently of cytosolic waves under certain conditions.