Activity-dependent targeting of TRPV1 with a pore-permeating capsaicin analog.

ABSTRACT: The capsaicin receptor TRPV1 is the principal transduction channel for nociception. Excessive TRPV1 activation causes pathological pain. Ideal pain mangement requires selective inhibition of hyperactive pain-sensing neurons, but sparing normal nociception. We sought to determine whether it is possible to use activity-dependent TRPV1 agonists to identify nerves with excessive TRPV1 activity, as well as exploit the TRPV1 pore to deliver charged anesthetics for neuronal silencing. We synthesized a series of permanently charged capsaicinoids and found that one, cap-ET, efficaciously evoked TRPV1-dependent entry of Ca(2+) or the large cationic dye YO-PRO-1 comparably to capsaicin, but far smaller electrical currents. Cap-ET-induced YO-PRO-1 transport required permeation of both the agonist and

SUBMITTER: Li H 

PROVIDER: S-EPMC3100990 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature