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

Abstract

Ren Z, Rhyu M, Phan TT, Mummalaneni S, Murthy KS, Grider JR, DeSimone JA, Lyall V. TRPM5-dependent amilorideand benzamil-insensitive NaCl chorda tympani taste nerve response. Am J Physiol Gastrointest Liver Physiol 305: G106 -G117, 2013. First published May 2, 2013; doi:10.1152/ajpgi.00053.2013.-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 ϩ 5 M Bz (NaCl ϩ 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 ϩ Bz ϩ RTX CT responses were also monitored in the presence of triphenylphosphine oxide, a specific TRPM5 blocker, and capsazepine and N-(3-methoxyphenyl)-4-chlorocinnamid (SB-366791), specific TRPV1 blockers. In rats and WT mice, RTX produced biphasic effects on the NaCl ϩ Bz CT response, enhancing the response at 0.5-1 M and inhibiting it at Ͼ1 M. The NaCl ϩ Bz ϩ SB-366791 CT response in rats and WT mice and the NaCl ϩ 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 ϩ 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 ϩ Bz tonic CT response. The relationship between RTX concentration and the magnitude of the tonic NaCl ϩ 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. triphenylphosphine oxide; resiniferatoxin; capsazepine; SB-366791; TRPV1 APPETITIVE AND AVERSIVE NEURAL and behavioral responses to NaCl are most likely transduced by a variety of mechanisms (35). Several studies suggest that in the anterior tongue Na ϩ from a Na ϩ salt taste stimulus enters a subset of taste bud cells by at least two types of cation channels located in taste cell apical membranes. One channel type is the Na ϩ -specific epithelial Na ϩ channel (ENaC), in which Na ϩ transport is inhibited by amiloride and benzamil (Bz) (1, 3, 8). The second involves Na ϩ transport through a putative transient receptor potential (TRP) vanilloid subfamily member 1 (TRPV1t)-nonspecific cation channel (26,27). The TRPV1t channel is insensitive to amiloride and Bz, permeable to Na ϩ , K ϩ , NH 4 ϩ , and Ca 2ϩ , and contributes to cell depolarization (31). These conclusions are supported by the observations that the phasic (transient) and tonic (steady-state) components of ...

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