Histamine potentiates IP(3)-mediated Ca(2+) release via thapsigargin-sensitive Ca(2+) pumps

Area of Science:

• Cell Biology
• Molecular Pharmacology
• Calcium Signaling

Background:

• Histamine is a known signaling molecule.
• Inositol 1,4,5-trisphosphate (IP3) mediates calcium (Ca2+) release from intracellular stores.
• The interplay between histamine signaling and IP3-mediated Ca2+ release is not fully understood.

Purpose of the Study:

• To investigate the mechanism of histamine-induced potentiation of IP3-mediated Ca2+ release in HeLa cells.
• To determine the role of cellular structures and SERCA pumps in this potentiation.

Main Methods:

• HeLa cells were used for experiments.
• Inositol 1,4,5-trisphosphate (IP3) was dialyzed into cells to increase intracellular levels.
• Patch-clamp technique was employed to measure Ca2+ release.
• Effects of histamine, cytochalasin D, colchicine, and thapsigargin were assessed.

Main Results:

• Low concentrations of histamine accelerated IP3-mediated Ca2+ release, requiring concurrent histamine signaling and elevated IP3.
• Disrupting microfilaments (cytochalasin D) and microtubules (colchicine) reduced the histamine response and IP3-mediated Ca2+ release rate.
• Inhibiting SERCA pumps with thapsigargin diminished histamine-induced potentiation without affecting the basal IP3-mediated Ca2+ release rate.

Conclusions:

• Histamine potentiation of Ca2+ release in HeLa cells is not solely due to increased IP3 levels.
• Active SERCA pumps are crucial for the histamine-induced potentiation of IP3-mediated Ca2+ release.
• SERCA pumps play a significant role in regulating the efficiency of agonist-induced Ca2+ release.