Ca(2+) entry activated by S-nitrosylation. Relationship to store-operated ca(2+) entry

Area of Science:

• Cellular Physiology
• Molecular Biology
• Calcium Signaling

Background:

• The precise coupling mechanism between intracellular calcium (Ca2+) pools and store-operated Ca2+ entry channels (SOCs) is not fully understood.
• Previous research indicated that Ca2+ entry can be activated by S-nitrosylation, a process enhanced by Ca2+ pool depletion.

Purpose of the Study:

• To investigate the relationship between S-nitrosylation-activated Ca2+ entry and store-operated Ca2+ entry (SOC) mechanisms.
• To determine if S-nitrosylation directly modifies Ca2+ entry channels or their regulatory components.

Main Methods:

• Utilized smooth muscle cells (DDT1MF-2) and fibroblasts (DC-3F) to study Ca2+ entry.
• Employed the NO donor GEA3162 and the alkylator N-ethylmaleimide to induce S-nitrosylation.
• Assessed Ca2+ entry activation by transient external Ca2+ removal and its modulation by actin cytoskeleton disruption (Calyculin A).

Main Results:

• Ca2+ entry activated by NO donors or alkylators was strongly enhanced by Ca2+ removal, similar to SOC activation.
• Non-additivity of SOC and NO donor-activated entry suggested a shared entry pathway.
• Actin cytoskeleton disruption inhibited SOC but not GEA3162-induced Ca2+ entry, while differences in Ba2+ entry and La3+ sensitivity were noted.

Conclusions:

• S-nitrosylation may directly modify Ca2+ entry channels, bypassing the typical coupling with Ca2+ pools.
• This S-nitrosylation-mediated entry mechanism is closely related to SOC activity.
• In some cell types, S-nitrosylation may regulate SOC or directly impact the entry channel itself.