Aquaporin-1 tunes pain perception by interaction with Na(v)1.8 Na+ channels in dorsal root ganglion neurons.
Aquaporin-1 (AQP1) water channels are expressed in the plasma membrane of dorsal root ganglion (DRG) neurons. We found reduced osmotic water permeability in freshly isolated DRG neurons from AQP1(-/-) versus AQP1(+/+) mice. Behavioral studies showed greatly reduced thermal inflammatory pain perception in AQP1(-/-) mice evoked by bradykinin, prostaglandin E(2), and capsaicin as well as reduced cold pain perception. Patch clamp of freshly isolated DRG neurons showed reduced action potential firing in response to current injections. Single action potentials after pulse current injections showed reduced maximum inward current, suggesting impaired Na(v)1.8 Na(+) function. Whole-cell Na(v)1.8 Na(+) currents in Na(v)1.8-expressing ND7-23 cells showed slowed frequency-dependent inactivation after AQP1 transfection. Immunoprecipitation studies showed AQP1- Na(v)1.8 Na(+) interaction, which was verified in live cells by single-particle tracking of quantum dot-labeled AQP1. Our results implicate the involvement of AQP1 in DRG neurons for the perception of inflammatory thermal pain and cold pain, whose molecular basis is accounted for, in part, by reduced Na(v)1.8-dependent membrane Na(+) current. AQP1 is, thus, a novel target for pain management.
Zhang
Hua
H
Department of Medicine, University of California, San Francisco, California 94143-0521, USA.
Verkman
A S
AS
D000200:Action Potentials; D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism*; D001920:Bradykinin / Q000009:adverse effects / Q000494:pharmacology; D002211:Capsaicin / Q000009:adverse effects / Q000494:pharmacology; D045744:Cell Line, Tumor; D015232:Dinoprostone / Q000009:adverse effects / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009474:Neurons / Q000378:metabolism*; D010120:Oxytocics / Q000009:adverse effects / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D059408:Pain Management; D010465:Perception / Q000187:drug effects; D018689:Sensory System Agents / Q000009:adverse effects / Q000494:pharmacology; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D014665:Vasodilator Agents / Q000009:adverse effects / Q000494:pharmacology
C496021:Aqp1 protein, mouse; D062559:NAV1.8 Voltage-Gated Sodium Channel; D010120:Oxytocics; C568318:Scn10a protein, mouse; D018689:Sensory System Agents; D015222:Sodium Channels; D014665:Vasodilator Agents; D051398:Aquaporin 1; D015232:Dinoprostone; D002211:Capsaicin; D001920:Bradykinin