Related Experiment Video
Updated: Jun 5, 2026
09:43
Functional and Morphological Assessment of Diaphragm Innervation by Phrenic Motor Neurons
Published on: May 25, 2015
Spinal 5-HT7 receptor activation induces long-lasting phrenic motor facilitation
1Department of Comparative Biosciences, University of Wisconsin, 2015 Linden Drive, Madison, WI, 53706, USA.
The Journal of Physiology
|January 19, 2011
Summary
Serotonin-7 (5-HT7) receptor activation in the spinal cord causes long-lasting phrenic motor facilitation (PMF) through TrkB receptor synthesis. This finding offers potential therapeutic strategies for respiratory control disorders.
Area of Science:
- Neuroscience
- Respiratory Physiology
- Pharmacology
Background:
- Acute intermittent hypoxia induces serotonin-dependent respiratory plasticity (phrenic long-term facilitation, pLTF).
- pLTF requires serotonin-2 (5-HT2) receptor activation and brain-derived neurotrophic factor (BDNF) synthesis.
- Gs protein-coupled adenosine 2A receptors (GsPCRs) activate phrenic motor facilitation (PMF) via BDNF-independent TrkB trans-activation.
Purpose of the Study:
- To investigate if other GsPCRs, specifically serotonin-7 (5-HT7) receptors, can elicit PMF.
- To elucidate the signaling mechanisms underlying 5-HT7 receptor-mediated PMF.
Main Methods:
- Administration of a selective 5-HT7 receptor agonist (AS-19) or antagonist (SB 269970) via cervical spinal injections in anesthetized rats.
- Inhibition of TrkB receptor synthesis and activity using a TrkB inhibitor (k252a) and siRNAs.
- Assessment of the involvement of PI3K/AKT and MEK/ERK signaling pathways.
Main Results:
- Selective 5-HT7 receptor activation elicited long-lasting PMF (>120 min).
- 5-HT7 receptor-mediated PMF was blocked by 5-HT7 receptor antagonist pretreatment.
- PMF induction required TrkB synthesis and activity, with late-phase PMF specifically affected by TrkB inhibition.
- Spinal PI3K/AKT pathway inhibition blocked PMF, while MEK/ERK inhibition only delayed it.
Conclusions:
- Spinal 5-HT7 receptors are sufficient to induce long-lasting PMF.
- 5-HT7 receptor-mediated PMF involves TrkB receptor synthesis and activation, distinct from BDNF-dependent pathways.
- The PI3K/AKT pathway is crucial for 5-HT7 receptor-induced PMF, suggesting novel therapeutic targets for respiratory control disorders.
Related Concept Videos
01:23Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists
Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...
01:30Parasympathetic Signaling
Parasympathetic signaling plays a crucial role in regulating various physiological processes. It involves the release of acetylcholine (ACh) by parasympathetic neurons, which can have localized and short-lived effects. The majority of ACh released is rapidly inactivated at the synapse by the enzyme acetylcholinesterase (AChE), which hydrolyzes Ach into choline and acetate. Additionally, the tissue cholinesterase deactivates any ACh diffusing into the surrounding tissues.
The effects of...
The effects of...
01:29Relaxation of Skeletal Muscles
The period of muscle contraction primarily influences the duration of stimulation at the neuromuscular junction (NMJ), the presence of free calcium ions in the sarcoplasm, and the availability of energy or ATP to support contractions.
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated sodium channels. Sodium ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated calcium channels to open.
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated sodium channels. Sodium ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated calcium channels to open.
01:22Somatic Spinal Reflexes
Somatic spinal reflexes are rapid, involuntary muscular responses to external stimuli that involve the somatic musculature and the spinal cord.
One of the most well-known somatic spinal reflexes is the stretch reflex, which is activated by the sudden stretching of a muscle. This reflex involves the activation of specialized sensory receptors called muscle spindles, which are located in the muscle tissue and detect changes in the length and speed of muscle contractions. When a muscle is suddenly...
One of the most well-known somatic spinal reflexes is the stretch reflex, which is activated by the sudden stretching of a muscle. This reflex involves the activation of specialized sensory receptors called muscle spindles, which are located in the muscle tissue and detect changes in the length and speed of muscle contractions. When a muscle is suddenly...
01:25Cholinergic Receptors: Muscarinic
The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine.
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+. Activation...
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+. Activation...
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...