The voltage-gated sodium channel Nav1.9 is required for inflammation-based urinary bladder dysfunction
Amy M Ritter1, William J Martin, Kevin S Thorneloe
1Department of Immunology, Merck Research Labs, Rahway, NJ 06070, United States. a_m_ritter@hotmail.com
Neuroscience Letters
|January 17, 2009
Summary
The Nav1.9 sodium channel is crucial for inflammatory pain in the bladder. Nav1.9 knockout mice showed no bladder dysfunction during inflammation, unlike wildtype mice.
Area of Science:
- Neuroscience
- Urology
- Pain Research
Background:
- Tetrodotoxin (TTX)-resistant sodium channels, particularly Nav1.9, are implicated in inflammatory pain.
- These channels are present in small diameter primary sensory neurons.
Purpose of the Study:
- To investigate the role of the Nav1.9 voltage-gated sodium channel in bladder dysfunction during inflammation.
- To examine the contribution of Nav1.9 to inflammation-based bladder dysfunction using knockout mouse models.
Main Methods:
- Urodynamic analysis of Nav1.9 knockout (KO) and wildtype (WT) mice.
- Peripheral nerve recordings from pelvic afferents.
- Sensitization assessment using intravesical prostaglandin E2 (PGE2).
- In vivo cyclophosphamide treatment to induce inflammation.
Main Results:
- No significant differences in basal urodynamics between WT and Nav1.9 KO mice.
- Nav1.9 KO mice lacked sensitization of pelvic afferents to PGE2.
- Cyclophosphamide-induced reduction in bladder capacity was observed in WT but not in Nav1.9 KO mice.
Conclusions:
- The Nav1.9 sodium channel plays a key role in linking inflammatory processes to altered urodynamic function in the urinary bladder.
- Nav1.9 is essential for the development of inflammation-induced bladder dysfunction.
Related Concept Videos
01:26Voltage-gated Ion Channels
Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
01:26Voltage-gated Ion Channels
Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
01:12Mechanically-gated Ion Channels
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
01:24Non-gated Ion Channels
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
01:19Ion Channels
The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow specific...
Ion channels are specialized integral membrane proteins on the plasma membrane that allow specific...