I(ARC), a novel arachidonate-regulated, noncapacitative Ca(2+) entry channel

Area of Science:

• Cellular Biology
• Physiology
• Biochemistry

Background:

• Intracellular calcium (Ca2+) signals are crucial for cellular functions, involving both release from stores and entry from extracellular space.
• Receptor-activated Ca2+ entry is essential for generating these signals, particularly via phospholipase C activation.
• Existing models of Ca2+ entry, like capacitative calcium entry, may not fully explain signaling at physiological agonist concentrations.

Purpose of the Study:

• To investigate the mechanism of Ca2+ entry at physiological agonist concentrations.
• To identify and characterize novel Ca2+ entry pathways involved in intracellular Ca2+ signaling.
• To differentiate this pathway from established store-operated Ca2+ entry mechanisms.

Main Methods:

• Whole-cell patch clamp electrophysiology was employed to record Ca2+ currents.
• Cells were stimulated with varying concentrations of arachidonic acid.
• The Ca2+ entry was assessed under conditions of both replete and depleted intracellular Ca2+ stores.

Main Results:

• A novel Ca2+-selective current, termed arachidonate-regulated calcium current (I(ARC)), was identified and activated by low concentrations of arachidonic acid.
• This current exhibits distinct features compared to the store-operated current I(CRAC).
• I(ARC) activation was observed even when intracellular Ca2+ stores were maximally depleted, indicating independence from store content.

Conclusions:

• Arachidonic acid regulates a distinct, non-capacitative Ca2+ entry pathway (I(ARC)) crucial for physiological signaling.
• I(ARC) represents a novel mechanism of Ca2+ influx, separate from store-operated pathways.
• This pathway is specifically activated under physiological stimulation conditions, offering new insights into cellular Ca2+ dynamics.