Extracellular acidification modifies Ca2+ fluxes in rat brain synaptosomes

Area of Science:

• Neuroscience
• Cell Physiology
• Biochemistry

Background:

• Calcium (Ca2+) homeostasis is crucial for neuronal function.
• Synaptosomes are vital for studying neurotransmitter release and neuronal signaling.
• External pH changes can significantly impact cellular processes.

Purpose of the Study:

• To investigate the effects of external acidification on Ca2+ fluxes in rat brain synaptosomes.
• To elucidate the mechanisms underlying Ca2+ flux alterations under acidic conditions.
• To determine the involvement of specific ion transporters and signaling pathways.

Main Methods:

• Measurement of 45Ca2+ influx and efflux in rat brain synaptosomes.
• Assessment of Na+ dependence and amiloride sensitivity of Ca2+ fluxes.
• Evaluation of Ca2+ channel blockers' effects on Ca2+ uptake.
• Analysis of phosphoinositide hydrolysis in response to pH changes.
• Investigation of neomycin's impact on Ca2+ fluxes.

Main Results:

• External acidification (pH 7.5 to 6.5) linearly decreased 45Ca2+ uptake and increased 45Ca2+ efflux.
• Ca2+ flux changes were Na+ dependent and amiloride sensitive, suggesting Na+/Ca2+ exchanger involvement.
• Ca2+ channel blockers did not affect acid-evoked Ca2+ uptake reduction.
• Acidic pH stimulated phosphoinositide hydrolysis, an amiloride-insensitive process.
• Neomycin inhibited the effects of acidic pH on Ca2+ fluxes.

Conclusions:

• External acidification stimulates phospholipase C, increasing phosphoinositide hydrolysis and intracellular Ca2+ mobilization.
• Increased intracellular Ca2+ activates the Na+/Ca2+ exchanger, leading to enhanced Ca2+ efflux.
• Acidification reduces global Ca2+ influx indirectly by increasing intracellular Ca2+ concentration.
• Voltage-sensitive Ca2+ channels are not involved in the observed Ca2+ influx changes during acidification.