RESEARCH ARTICLE


Effects of PKC and PKA Inhibitors on the cAMP-Stimulant-Induced Enhancement of Tetrodotoxin-Resistant Na+ (Nav1.8) Currents



Shigeji Matsumoto*, Shinki Yoshida, Mizuho Ikeda, Chikako Saiki , Mamoru Takeda
Department of Physiology, Nippon Dental University, School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan


© 2008 Matsumoto et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Correspondence: * Address correspondence to this author at the Department of Physiology, Nippon Dental University, School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan; el: +81 3 3261 8706; Fax: +81 3 3261 8740; E-mail: matsu-s@tky.ndu.ac.jp


Abstract

The protein kinase C (PKC) inhibitor bisindolymaleimide Ro-31-8425 (Ro-31-8425) decreases the peak tetrodotoxin- resistant (TTX-R) Na+ (Nav1.8) current in nodose ganglion (NG) neurons, and this decrease is not altered by simultaneous application of 8-bromo-cAMP (8-Br-cAMP), phorbol 12-myristate 13-acetate (PMA, a PKC activator) or forskolin (a cAMP analogue). Intracellular application of the endogenous protein kinase A (PKA) inhibitor, protein kinase inhibitor (PKI) abolishes the increase in the peak Nav1.8 current that occurs in response to the applications of 8-BrcAMP, PMA, forskolin, or prostaglandin E2 (PGE2, an adenyl cyclase activator). At a higher concentration (0.5 mM) compared with a sufficient concentration (0.01 mM) to block the cAMP-stimulant Nav1.8 current, PKI still attenuated the Ro-31-8425-induced decrease in peak Nav1.8 current. When we considered these results together, cAMP-stimulantinduced modification of Nav1.8 currents is mediated by the activation of both PKA and PKC, and PKC may be located upstream of PKA.