Cyclosporin A and deltamethrin block the downregulation of Nav1.8 sodium channels expressed in Xenopus oocytes.
The Nav1.8 sodium channel isoform, expressed in sensory neurons and implicated in pain responses, is known to be upregulated in Xenopus oocytes by agents that activate protein kinase A. In the absence of exogenous modulators, Nav1.8 channels expressed in oocytes exhibited spontaneous downregulation, so that the amplitudes of peak sodium currents at the end of a 30-min recording period were reduced to 58% of those at the outset of recording with no change in the properties of the expressed channels. Perfusion of oocytes with either cyclosporin A or deltamethrin, considered to be diagnostic inhibitors of the protein phosphatase calcineurin, at 10 microM blocked spontaneous downregulation. These results identify endogenous calcineurin as the mediator of Nav1.8 sodium channel downregulation in oocytes. The use of a calcineurin inhibitor such as cyclosporin A provides an effective means of stabilizing the expression of Nav1.8 sodium channels in oocytes for functional and pharmacological studies.
Choi
Jin-Sung
JS
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Soderlund
David M
DM
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009570:Nitriles; D009865:Oocytes / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D011722:Pyrethrins / Q000494:pharmacology*; D015222:Sodium Channels / Q000378:metabolism*; D013997:Time Factors; D014981:Xenopus
D004791:Enzyme Inhibitors; D009570:Nitriles; D011722:Pyrethrins; D015222:Sodium Channels; C017180:decamethrin; C017498:cismethrin; D016572:Cyclosporine