Plasticity of the peripheral taste system: Functional dissection of salt transduction pathways

It is established that, extracellular Ca{dollar}sp{lcub}+2{rcub}{dollar} above a critical concentration, modulates the permeability of paracellular pathways in various epithelia by up-regulating the degree of sealing of the tight junctions (TJs). Ca{dollar}sp{lcub}+2{rcub}{dollar}-induced modulation of the TJs is associated with Ca{dollar}sp{lcub}+2{rcub}{dollar} binding to fixed negative sites. This results in a conversion of tight-junctional ion selectivity from cationic to anionic. We have observed the Ca{dollar}sp{lcub}+2{rcub}{dollar}-induced conversion of junctional ion-exchange characteristics in the taste system, through simultaneous monitoring of the lingual transepithelial potential (TEP) while recording from the chorda tympani (CT) taste nerves in the rat. Unlike most other salts, CaCl{dollar}sb2{dollar} induced negatively-directed changes in the TEP, and gave CT responses that were auto-inhibitory beyond a critical concentration. CaCl{dollar}sb2{dollar} CT responses increased in a dose-dependent manner to approximately 0.3 M, decreased with further increases in concentration. At concentrations where Ca{dollar}sp{lcub}+2{rcub}{dollar} was self-inhibitory, it also inhibited responses to NaCl, KCl, and NH{dollar}sb4{dollar}Cl in mixtures with CaCl{dollar}sb2.{dollar} Specifically, Ca{dollar}sp{lcub}+2{rcub}{dollar} blocked (1) the amiloride-insensitive component of the NaCl CT response, (2) the entire KCl CT response, and (3) responses to high concentrations of NH{dollar}sb4{dollar}Cl ({dollar}>{dollar}0.3 M). Below 0.3 M, NH{dollar}sb4{dollar}Cl responses exhibit low Ca{dollar}sp{lcub}+2{rcub}{dollar} sensitivity, suggesting independent transduction sites. The similar Ca{dollar}sp{lcub}+2{rcub}{dollar}-sensitivity of the CT responses to the Cl{dollar}sp-{dollar} salts of Na{dollar}rmsp+, Ksp+,{dollar} and NH{dollar}sb4sp+{dollar} suggests a common transduction pathway and further indicates that transduction sites for NaCl, KCl, and NH{dollar}sb4{dollar}Cl taste reception are accessible only through the paracellular pathways. The concentration dependence of the CT response to NH{dollar}sb4{dollar}Cl is biphasic and non-linear, unlike those to KCl or NaCl. Up to 0.3 M, the CT response increases. This kinetic profile is Cl{dollar}sp-{dollar} dependent and is correlated with an increase in transepithelial conductance (TEC) that displays a similar NH{dollar}sb4{dollar}Cl concentration-dependence. Unlike neural responses to KCl, but similar to NaCl, those to NH{dollar}sb4{dollar}Cl were voltage sensitive. Amiloride partially suppressed CT responses within the NH{dollar}sb4{dollar}Cl concentration range 0.05-0.3 M. Amiloride also suppressed the voltage sensitivity of NH{dollar}sb4{dollar}Cl CT responses. In conclusion, the data suggest that taste transduction for NH{dollar}sb{lcub}4sp-{rcub}{dollar} salts is mediated over two NH{dollar}sb4sp+{dollar} conduction pathways: transcellular and paracellular.