The Effect of Doxapram on Proprioceptive Neurons: Invertebrate Model.
Bethany J Ison1, Maya O Abul-Khoudoud1, Sufia Ahmed1
1Department of Biology, University of Kentucky, Lexington, KY 40506, USA.
Neurosci
|November 1, 2024
Summary
Doxapram enhances neural excitation at low doses but over-excites crustacean neurons at high concentrations, impacting K2p channels. Verapamil reduces neural activity, potentially affecting multiple ion channels.
Area of Science:
- Neuroscience
- Pharmacology
- Crustacean biology
Background:
- Resting membrane potential is crucial for neuronal electrical signaling and excitability.
- Potassium two pore domain (K2p) channels are vital for maintaining resting membrane potential.
- Doxapram is a known pH-sensitive K2p channel blocker.
Purpose of the Study:
- To investigate the effects of doxapram and verapamil on neural activity in blue crab walking leg sensory neurons.
- To explore the potential of K2p channels as a target for pharmacological agents in crustaceans.
Main Methods:
- Assessed neural activity in the propodite-dactylopodite (PD) sensory organ of Callinectes sapidus.
- Applied varying concentrations (0.1 mM and 5 mM) of doxapram and verapamil.
- Utilized whole nerve preparations to analyze compound action potentials.
Main Results:
- 0.1 mM doxapram enhanced neural excitation.
- 5 mM doxapram led to over-excitation and a sustained refractory period, mimicking high potassium (K+) exposure.
- Verapamil (0.1 and 5 mM) reduced neural activity, possibly by blocking stretch-activated channels and L-type Ca2+ channels.
Conclusions:
- Doxapram exhibits acute effects on crustacean neurons, suggesting a specific K2p channel target.
- Verapamil's actions are complex, potentially involving multiple ion channel types.
- Crustacean neurons serve as a valuable model for understanding pharmacological agent mechanisms.
