Cholesterol regulates polymodal sensory transduction in Müller glia
Abstract
Over‐ and underexposure to cholesterol activates glia in neurodegenerative brain and retinal diseases but the molecular targets of cholesterol in glial cells are not known. Here, we report that disruption of unesterified membrane cholesterol content modulates the transduction of chemical, mechanical and temperature stimuli in mouse Müller cells. Activation of TRPV4 (transient receptor potential vanilloid type 4), a nonselective polymodal cation channel was studied following the removal or supplementation of cholesterol using the methyl‐beta cyclodextrin (MβCD) delivery vehicle. Cholesterol extraction disrupted lipid rafts and caveolae without affecting TRPV4 trafficking or membrane localization protein. However, MβCD suppressed agonist (GSK1016790A)‐ and temperature‐evoked elevations in [Ca2+]i, and suppressed transcellular propagation of Ca2+ waves. Lowering the free membrane cholesterol content markedly prolonged the time‐course of the glial swelling response, whereas MβCD:cholesterol supplementation enhanced agonist‐ and temperature‐induced Ca2+ signals and shortened the swelling response. Taken together, these data show that membrane cholesterol modulates polymodal transduction of agonists, swelling and temperature stimuli in retinal radial glia and suggest that dyslipidemic retinas might be associated with abnormal glial transduction of ambient sensory inputs.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 30, 2017
- Source ID
- 10.1002/glia.23213
Entities
People
- Anthony Iuso
- David Križaj
- Jackson M. Baumann
- Monika Lakk
- Oleg Yarishkin
Organizations
- National Institutes of Health
- Research to Prevent Blindness
- United States Department of Defense
- University of Utah