Phrenic motor neuron adenosine 2A receptors elicit phrenic motor facilitation

J Physiol, 2018 · DOI: 10.1113/JP275462 · Published: January 31, 2018

Simple Explanation

Adenosine 2A (A2A) receptors are activated to trigger cell signaling cascades; however, the physiological results depend on the type of cell that has these receptors. Activating A2A receptors in the cervical spinal cord causes a lasting increase in phrenic nerve activity. This effect was almost eliminated by injecting A2A receptor siRNA into the chest cavity. The study suggests that increasing A2A receptor expression in phrenic motor neurons could be a way to improve their excitability in conditions like spinal cord injury.

Study Duration

7 days

Participants

34 adult male Sprague–Dawley rats

Evidence Level

Level 2: Experimental study using animal models

Key Findings

1
A2A receptors are highly expressed in motor neurons (including phrenic motor neurons) versus other cell types in the cervical spinal cord.
2
Intrapleural siA2A injections selectively knock down A2A receptor expression in phrenic motor neurons and strongly attenuate A2A receptor-induced pMF.
3
The relevant receptors for A2A receptor-induced pMF are within phrenic motor neurons per se, at least in normal rats.

Research Summary

The study investigates the specific cervical spinal cells expressing A2A receptors responsible for phrenic motor facilitation (pMF). The researchers used siRNA injections to knock down A2A receptors in phrenic motor neurons, observing a significant reduction in A2A receptor immunoreactivity within these neurons. The study concludes that A2A receptors within phrenic motor neurons are responsible for A2A receptor-induced pMF, at least in normal rats.

Practical Implications

Therapeutic Target Identification

A2A receptors in phrenic motor neurons are potential therapeutic targets for enhancing respiratory function in neuromuscular disorders.

Spinal Cord Injury Treatment

Upregulating A2A receptors in phrenic motor neurons may compensate for reduced excitatory inputs after cervical spinal cord injury, improving breathing.

Understanding Adenosine Antagonists

Commonly used adenosine receptor antagonists like caffeine may undermine neuroplasticity in specific pathological states, requiring careful consideration.

Study Limitations

1
Study was conducted on normal rats, and results may vary in pathological conditions.
2
The study only observed a knock-down, not a complete knock-out, of A2A receptors.
3
Distal dendrite contributions of non-phrenic motor neurons cannot be completely ruled out.

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