Changes in Taste Receptor Cell [ca Salty and Sour Taste Stimuli 2 3 Running Title: Regulation of Salty and Sour Ct Responses by [ca

23 Relationship between taste receptor cell (TRC) Ca ([Ca]i) and rat chorda 24 tympani (CT) nerve responses to salty (NaCl and NaCl+benzamil (Bz)) and sour (HCl, 25 CO2 and acetic acid) taste stimuli was investigated before and after lingual application 26 of ionomycin+Ca, 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid tetrakis27 (acetoxymethyl ester) (BAPTA-AM), U73122 (phospholipase C blocker) and 28 thapsigargin (Ca-ATPase inhibitor) under open circuit or lingual voltage clamp 29 conditions. An increase in TRC [Ca]i attenuated the tonic Bz-sensitive NaCl CT 30 response and the apical membrane Na conductance. A decrease in TRC [Ca]i 31 enhanced the tonic Bz-sensitive and Bz-insensitive NaCl CT responses and apical 32 membrane Na conductance but did not affect CT responses to KCl or NH4Cl. An 33 increase in TRC [Ca]i did not alter the phasic response but attenuated the tonic CT 34 response to acidic stimuli. A decrease in [Ca]i did not alter the phasic response but 35 attenuated the tonic CT response to acidic stimuli. In a subset of TRCs a positive 36 relationship between [H]i and [Ca]i was obtained using in vitro imaging techniques. 37 U73122 inhibited the tonic CT responses to NaCl and thapsigargin inhibited the tonic 38 CT responses to salty and sour stimuli. The results suggest that salty and sour taste 39 qualities are transduced by [Ca]i-dependent and [Ca]i-independent mechanisms. 40 Changes in TRC [Ca]i in BAPTA-sensitive cytosolic compartment regulate ion 41 channels and co-transporters involved in the salty and sour taste transduction 42 mechanisms and in neural adaptation. Changes in TRC [Ca]i in a separate sub43 compartment, sensitive to inositol trisphosphate and thapsigargin, but inaccessible to 44 BAPTA, are associated with neurotransmitter release. 45