ATP causes glomus cell [Ca2+]c increase without corresponding increases in CSN activity

Area of Science:

• Neuroscience
• Cell Physiology
• Biochemistry

Background:

• The carotid body (CB) is a chemosensory organ crucial for regulating breathing.
• Intracellular calcium ([Ca(2+)](c)) plays a key role in CB sensory transduction.
• The precise relationship between [Ca(2+)](c) and carotid sinus nerve (CSN) activity is not fully understood.

Purpose of the Study:

• To investigate the effect of extracellular ATP on intracellular calcium levels in rat CB glomus cells.
• To determine the impact of ATP-induced [Ca(2+)](c) changes on afferent CSN activity.

Main Methods:

• In vitro rat carotid body preparation.
• Measurement of intracellular calcium using fluorescent indicators.
• Extracellular application of ATP at various concentrations.
• Electrophysiological recordings of CSN activity and glomus cell membrane potential.
• Pharmacological manipulation using Suramin and cyclopiazonic acid (CPA).

Main Results:

• ATP caused a dose-dependent increase in [Ca(2+)](c), with 2/3 from influx and 1/3 from ER release.
• Low ATP concentrations (5-10 microM) stimulated CSN activity under normoxia and hypoxia.
• High ATP concentrations (≥100 microM) initially stimulated but then inhibited CSN activity.
• ATP-induced glomus cell hyperpolarization and increased outward K+ current were observed at 100 microM ATP.

Conclusions:

• ATP-evoked intracellular calcium increases do not linearly correlate with CSN activity.
• High ATP concentrations may inhibit CSN activity via mechanisms involving K+ currents and hyperpolarization.
• The study challenges the simple hypothesis linking [Ca(2+)](c) rise directly to enhanced CSN activity.