Effects of protein kinase C on the Na(+)-H+ exchange in the cochlear outer hair cell.
Two routes, associated with protein kinase C (PKC) and cyclic AMP (cAMP), to regulate the activation of Na(+)-H+ exchange (NHE) were investigated in the outer hair cell (OHC). The intracellular pH (pHi) of OHC loaded with the pHi indicator dye was measured by using fluorescence ratio imaging microscopy. The acid load was carried out by an "NH4Cl pre-pulse". The rate of acid extrusion after an acid load was increased as pHi became more acidic. The linear relationship between the rate of acid extrusion and pHi suggests the presence of an internal modifier site for the H+ ion on the NHE. Although addition of phorbol 12-myristate 13-acetate (TPA) had no effect on pHi in unstimulated conditions, the pHi recovery from an acid load was enhanced by exposure to TPA. This finding can be explained by the pHi dependence of the PKC action, namely, that the activating effect of PKC on the NHE is facilitated by internal acidification. In contrast to the PKC effect, addition of dibutyryl cAMP failed to change the rate of acid extrusion. These findings are consistent with the characteristic property of the NHE-1. Thus, intracellular signal transduction to regulate the activity of the NHE in the OHC involves phosphorylation by PKC.
Ikeda
K
K
Department of Otorhinolaryngology, Tohoku University School of Medicine, Sendai, Japan.
Sunose
H
H
Takasaka
T
T
D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology*; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects*; D011493:Protein Kinase C / Q000494:pharmacology*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
D017923:Sodium-Hydrogen Exchangers; D000242:Cyclic AMP; D011493:Protein Kinase C