| Autor: |
Nakazawa Y; Faculty of Pharmacy, Keio University, 1-5-30 Shibako Minato-ku, Tokyo 105-8512, Japan., Petrova RS; Department of Physiology, School of Medical Sciences, New Zealand Eye Centre, University of Auckland, 85 Park Road, Auckland 1023, New Zealand., Sugiyama Y; Faculty of Pharmacy, Keio University, 1-5-30 Shibako Minato-ku, Tokyo 105-8512, Japan., Nagai N; Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan., Tamura H; Faculty of Pharmacy, Keio University, 1-5-30 Shibako Minato-ku, Tokyo 105-8512, Japan., Donaldson PJ; Department of Physiology, School of Medical Sciences, New Zealand Eye Centre, University of Auckland, 85 Park Road, Auckland 1023, New Zealand. |
| Abstrakt: |
Lens water transport generates a hydrostatic pressure gradient that is regulated by a dual-feedback system that utilizes the mechanosensitive transient receptor potential vanilloid (TRPV) channels, TRPV1 and TRPV4, to sense changes in mechanical tension and extracellular osmolarity. Here, we investigate whether the modulation of TRPV1 or TRPV4 activity dynamically affects their membrane trafficking. Mouse lenses were incubated in either pilocarpine or tropicamide to alter zonular tension, exposed to osmotic stress, or the TRPV1 and TRPV4 activators capsaicin andGSK1016790A (GSK101), and the effect on the TRPV1 and TRPV4 membrane trafficking in peripheral fiber cells visualized using confocal microscopy. Decreases in zonular tension caused the removal of TRPV4 from the membrane of peripheral fiber cells. Hypotonic challenge had no effect on TRPV1, but increased the membrane localization of TRPV4. Hypertonic challenge caused the insertion of TRPV1 and the removal of TRPV4 from the membranes of peripheral fiber cells. Capsaicin caused an increase in TRPV4 membrane localization, but had no effect on TRPV1; while GSK101 decreased the membrane localization of TRPV4 and increased the membrane localization of TRPV1. These reciprocal changes in TRPV1/4 membrane localization are consistent with the channels acting as mechanosensitive transducers of a dual-feedback pathway that regulates lens water transport. |
