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      • Regulatory Effects of Ca<sup>2+</sup> and H<sup>+</sup> on the Rat Chorda Tympani Response to NaCl and KCl

        DeSimone, John A.,Phan, Tam-Hao T.,Mummalaneni, Shobha,Rhyu, Mee-Ra,Heck, Gerard L.,Lyall, Vijay Oxford University Press 2015 Chemical senses Vol.40 No.6

        <P>Modulatory effects of pH<SUB>i</SUB> and [Ca<SUP>2+</SUP>]<SUB>i</SUB> on taste receptor cell (TRC) epithelial sodium channel (ENaC) were investigated by monitoring chorda tympani (CT) responses to NaCl and KCl at various lingual voltages, before and after lingual application of ionomycin and with 0–10mM CaCl<SUB>2</SUB> in the stimulus and rinse solutions adjusted to pH<SUB>o</SUB> 2.0–9.7. 0.1 and 0.5M KCl responses varied continuously with voltage and were fitted to an apical ion channel kinetic model using the same parameters. ENaC-dependent NaCl CT response was fitted to the same channel model but with parameters characteristic of ENaC. A graded increase in TRC [Ca<SUP>2+</SUP>]<SUB>i</SUB> decreased the ENaC-dependent NaCl CT response, and inhibited and ultimately eliminated its pH sensitivity. CT responses to KCl were pH<SUB>i</SUB>- and [Ca<SUP>2+</SUP>]<SUB>i</SUB>-independent. Between ±60 mV applied lingual potential, the data were well described by a linear approximation to the nonlinear channel equation and yielded 2 parameters, the open-circuit response and the negative of the slope of the line in the CT response versus voltage plot, designated the response conductance. The ENaC-dependent NaCl CT response conductance was a linear function of the open-circuit response for all pH<SUB>i</SUB>-[Ca<SUP>2+</SUP>]<SUB>i</SUB> combinations examined. Analysis of these data shows that pH<SUB>i</SUB> and [Ca<SUP>2+</SUP>]<SUB>i</SUB> regulate TRC ENaC exclusively through modulation of the maximum CT response.</P>

      • TRPM5-dependent amiloride- and benzamil-insensitive NaCl chorda tympani taste nerve response

        Ren, ZuoJun,Rhyu, Mee-Ra,Phan, Tam-Hao T.,Mummalaneni, Shobha,Murthy, Karnam S.,Grider, John R.,DeSimone, John A.,Lyall, Vijay American Physiological Society 2013 American journal of physiology, Gastrointestinal a Vol.305 No.1

        <P>Transient receptor potential (TRP) subfamily M member 5 (TRPM5) cation channel is involved in sensing sweet, bitter, umami, and fat taste stimuli, complex-tasting divalent salts, and temperature-induced changes in sweet taste. To investigate if the amiloride- and benzamil (Bz)-insensitive NaCl chorda tympani (CT) taste nerve response is also regulated in part by TRPM5, CT responses to 100 mM NaCl + 5 μM Bz (NaCl + Bz) were monitored in Sprague-Dawley rats, wild-type (WT) mice, and TRP vanilloid subfamily member 1 (TRPV1) and TRPM5 knockout (KO) mice in the presence of resiniferatoxin (RTX), a TRPV1 agonist. In rats, NaCl + Bz + RTX CT responses were also monitored in the presence of triphenylphosphine oxide, a specific TRPM5 blocker, and capsazepine and <I>N</I>-(3-methoxyphenyl)-4-chlorocinnamid (SB-366791), specific TRPV1 blockers. In rats and WT mice, RTX produced biphasic effects on the NaCl + Bz CT response, enhancing the response at 0.5–1 μM and inhibiting it at >1 μM. The NaCl + Bz + SB-366791 CT response in rats and WT mice and the NaCl + Bz CT response in TRPV1 KO mice were inhibited to baseline level and were RTX-insensitive. In rats, blocking TRPV1 by capsazepine or TRPM5 by triphenylphosphine oxide inhibited the tonic NaCl + Bz CT response and shifted the relationship between RTX concentration and the magnitude of the tonic CT response to higher RTX concentrations. TRPM5 KO mice elicited no constitutive NaCl + Bz tonic CT response. The relationship between RTX concentration and the magnitude of the tonic NaCl + Bz CT response was significantly attenuated and shifted to higher RTX concentrations. The results suggest that pharmacological or genetic alteration of TRPM5 activity modulates the Bz-insensitive NaCl CT response and its modulation by TRPV1 agonists.</P>

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