Salty taste deficits in CALHM1 knockout mice.
Genetic ablation of calcium homeostasis modulator 1 (CALHM1), which releases adenosine triphosphate from Type 2 taste cells, severely compromises the behavioral and electrophysiological responses to tastes detected by G protein-coupled receptors, such as sweet and bitter. However, the contribution of CALHM1 to salty taste perception is less clear. Here, we evaluated several salty taste-related phenotypes of CALHM1 knockout (KO) mice and their wild-type (WT) controls: 1) In a conditioned aversion test, CALHM1 WT and KO mice had similar NaCl avoidance thresholds. 2) In two-bottle choice tests, CALHM1 WT mice showed the classic inverted U-shaped NaCl concentration-preference function but CALHM1 KO mice had a blunted peak response. 3) In brief-access tests, CALHM1 KO mice showed less avoidance than did WT mice of high concentrations of NaCl, KCl, NH(4)Cl, and sodium lactate (NaLac). Amiloride further ameliorated the NaCl avoidance of CALHM1 KO mice, so that lick rates to a mixture of 1000 mM NaCl + 10 µM amiloride were statistically indistinguishable from those to water. 4) Relative to WT mice, CALHM1 KO mice had reduced chorda tympani nerve activity elicited by oral application of NaCl, NaLac, and sucrose but normal responses to HCl and NH(4)Cl. Chorda tympani responses to NaCl and NaLac were amiloride sensitive in WT but not KO mice. These results reinforce others demonstrating that multiple transduction pathways make complex, concentration-dependent contributions to salty taste perception. One of these pathways depends on CALHM1 to detect hypertonic NaCl in the mouth and signal the aversive taste of concentrated salt.
Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA, tordoff@monell.org.
Michael G
MG
Tordoff
Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA.
Hillary T
HT
Ellis
Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA.
Tiffany R
TR
Aleman
Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA.
Arnelle
A
Downing
Litwin-Zucker Research Center for the Study of Alzheimer's Disease, Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA.
Philippe
P
Marambaud
Department of Physiology, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
J Kevin
JK
Foskett
Department of Biology, Cooper Life Sciences Building, CL121, Ball State University, Muncie, IN 47306, USA and.
Rachel M
RM
Dana
Center for Medical Education, IUSM-Muncie at Ball State University, 221 N. Celia Avenue, MT 201, Muncie, IN 47306, USA.
Stuart A
SA
McCaughey
D000584:Amiloride / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D002814:Chorda Tympani Nerve / Q000502:physiology; D005260:Female; D005518:Food Preferences; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011189:Potassium Chloride / Q000378:metabolism; D012492:Salts / Q000378:metabolism*; D012965:Sodium Chloride / Q000378:metabolism; D019354:Sodium Lactate / Q000378:metabolism; D013649:Taste; D013650:Taste Buds / Q000502:physiology; D055697:Taste Perception
C575356:CALHM1 protein, mouse; D015220:Calcium Channels; D012492:Salts; D012965:Sodium Chloride; D011189:Potassium Chloride; D000584:Amiloride; D019354:Sodium Lactate
NaCl; gustatory electrophysiology; salt preference; salt taste