Effects of adenosine 5'-triphosphate and related agonists on cochlear function

Area of Science:

• Neuroscience
• Auditory Physiology
• Pharmacology

Background:

• Adenosine triphosphate (ATP) is implicated as a neurotransmitter or modulator in the cochlea.
• Previous research primarily used in vitro preparations, leaving in vivo effects largely unknown.

Purpose of the Study:

• To investigate the in vivo functional consequences of activating ATP receptors in the cochlea.
• To examine the effects of ATP and its analogs on cochlear and auditory nerve responses.
• To explore the in vitro effects on outer hair cell (OHC) currents and length.

Main Methods:

• In vivo assessment of cochlear microphonic (CM), summating potential (SP), distortion product otoacoustic emissions (DPOAE), and compound action potential (CAP) following local drug application.
• In vitro electrophysiological recordings of OHC currents and measurements of cell length.
• Testing of ATP and various agonist analogs, including ATP-gamma-S, ATP-alpha-S, 2-Me-S-ATP, and adenosine.

Main Results:

• In vivo, ATP-gamma-S significantly reduced CM, SP, DPOAE, and CAP, particularly at low to moderate stimulus intensities.
• High-intensity stimulation showed reduced suppression and increased SP with ATP-gamma-S.
• In vitro, ATP-gamma-S and ATP induced inward currents in OHCs without significant changes in cell length.

Conclusions:

• Endogenous ATP plays a role in modulating cochlear function via receptors at multiple cochlear sites.
• These modulatory effects are, at least partially, mediated by P2y receptors.