What drives calcium entry during [Ca2+]i oscillations?--challenging the capacitative model

Area of Science:

• Cellular Biology
• Molecular Physiology
• Biochemistry

Background:

• Agonist-activated receptors trigger intracellular calcium ([Ca2+]i) signals via the PLC/InsP3 pathway.
• Increased plasma membrane Ca2+ entry is essential for generating and sustaining these [Ca2+]i signals.
• Store-operated calcium entry (SOCE) is a well-established mechanism for sustained [Ca2+]i elevation at high agonist concentrations.

Purpose of the Study:

• To critically examine the assumption that SOCE underlies all agonist-enhanced Ca2+ entry.
• To investigate the mechanisms of Ca2+ entry during complex [Ca2+]i signals at physiological agonist levels.
• To present evidence challenging the universal applicability of the SOCE model.

Main Methods:

• Literature review and critical analysis of existing studies on agonist-activated Ca2+ entry.
• Comparison of the characteristics of SOCE with Ca2+ entry observed during physiological signaling.
• Examination of experimental evidence supporting or refuting the SOCE model in different cellular contexts.

Main Results:

• The role of SOCE in sustained, high-agonist-concentration [Ca2+]i signals is well-supported.
• Direct evidence for SOCE mediating Ca2+ entry during complex, physiological agonist stimulation is lacking.
• Key features of SOCE appear incompatible with its proposed role in certain types of agonist-activated Ca2+ signals.

Conclusions:

• The assumption that SOCE is the sole mechanism for agonist-enhanced Ca2+ entry requires re-evaluation.
• Alternative or additional mechanisms likely contribute to Ca2+ influx during physiological signaling.
• Further research is needed to elucidate the diverse pathways of agonist-activated Ca2+ entry.