Effect of cholesterol depletion on the pore dilation of TRPV1
Journal article, 2013

The TRPV1 ion channel is expressed in nociceptors, where pharmacological modulation of its function may offer a means of alleviating pain and neurogenic inflammation processes in the human body. The aim of this study was to investigate the effects of cholesterol depletion of the cell on ion-permeability of the TRPV1 ion channel. The ion-permeability properties of TRPV1 were assessed using whole-cell patch-clamp and YO-PRO uptake rate studies on a Chinese hamster ovary (CHO) cell line expressing this ion channel. Prolonged capsaicin-induced activation of TRPV1 with N-methyl-D-glucamine (NMDG) as the sole extracellular cation, generated a biphasic current which included an initial outward current followed by an inward current. Similarly, prolonged proton-activation (pH 5.5) of TRPV1 under hypocalcemic conditions also generated a biphasic current including a fast initial current peak followed by a larger second one. Patch-clamp recordings of reversal potentials of TRPV1 revealed an increase of the ion-permeability for NMDG during prolonged activation of this ion channel under hypocalcemic conditions. Our findings show that cholesterol depletion inhibited both the second current, and the increase in ion-permeability of the TRPV1 channel, resulting from sustained agonist-activation with capsaicin and protons (pH 5.5). These results were confirmed with YO-PRO uptake rate studies using laser scanning confocal microscopy, where cholesterol depletion was found to decrease TRPV1 mediated uptake rates of YO-PRO. Hence, these results propose a novel mechanism by which cellular cholesterol depletion modulates the function of TRPV1, which may constitute a novel approach for treatment of neurogenic pain.

MβCD

NMDG

YO-PRO

Ion-permeability

Cholesterol

Acidic pH

TRPV1

Capsaicin

Author

Erik Jansson

Chalmers, Chemical and Biological Engineering, Physical Chemistry

Carolina Trkulja

Chalmers, Chemical and Biological Engineering, Physical Chemistry

Aikeremu Ahemaiti

Chalmers, Chemical and Biological Engineering, Physical Chemistry

Maria Millingen

Chalmers, Chemical and Biological Engineering, Physical Chemistry

Gavin Jeffries

Chalmers, Chemical and Biological Engineering, Physical Chemistry

Kent Eric Jardemark

Chalmers, Chemical and Biological Engineering, Physical Chemistry

Owe Orwar

Chalmers, Chemical and Biological Engineering, Physical Chemistry

Molecular Pain

1744-8069 (ISSN)

Vol. 9 1 1

Subject Categories

Physical Chemistry

DOI

10.1186/1744-8069-9-1

More information

Created

10/7/2017