Interplay between Ca2+ release and Ca2+ influx underlies localized hyperpolarization-induced [Ca2+]i waves in...

Area of Science:

• Cell Biology
• Biophysics

Background:

• Calcium (Ca2+) acts as a crucial second messenger in regulating prostatic cell functions.
• The precise mechanisms controlling Ca2+ signaling in these cells remain incompletely understood.

Purpose of the Study:

• To investigate the spatiotemporal dynamics of Ca2+ signals in LNCaP cells, a model for androgen-dependent prostate cancer.
• To elucidate the mechanisms underlying the initiation and propagation of electrically induced Ca2+ waves.

Main Methods:

• Utilized non-invasive external electric field pulses to stimulate LNCaP cells.
• Employed high-speed fluo-3 confocal imaging to visualize intracellular Ca2+ ([Ca2+]i) dynamics.
• Applied Ca2+ entry blockers, thapsigargin (Ca2+-ATPase inhibitor), Mn2+ quenching, and InsP3 production inhibitors to probe signaling pathways.

Main Results:

• Electric field pulses initiated a rapidly propagated [Ca2+]i wave originating from the hyperpolarized membrane.
• The wave exhibited constant amplitude and an average velocity of approximately 20 microns/s.
• Wave initiation was dependent on localized Ca2+ influx and auto-regenerative Ca2+ release from stores.
• Wave progression involved the interplay between InsP3-sensitive Ca2+ store release and Ca2+ influx through channels activated by the Ca2+ rise.

Conclusions:

• Electrically induced Ca2+ waves in LNCaP cells are initiated by localized Ca2+ influx and regenerative Ca2+ release.
• The propagation of these waves requires coordinated Ca2+ release from InsP3-sensitive stores and subsequent Ca2+ influx.
• This study provides novel insights into the spatiotemporal control of Ca2+ signaling in prostatic cells.