Saccharin activates cation conductance via inositol 1,4,5-trisphosphate production in a subset of isolated rod taste cells in the frog.

The transduction mechanism of the conductance activated by saccharin was analysed in isolated bullfrog taste cells under whole-cell voltage-clamp. Bath application of 30 mM saccharin induced an inward current of -34 +/- 12 pA (mean +/- SEM, n = 10) at a membrane potential of -50 mV in 10 (23%) of 44 rod cells. The concentration-response relationship for the saccharin-gated current was consistent with that of the gustatory neural response. The saccharin-induced current was accompanied with a conductance increase under internal low Cl- condition (E(Cl) = -56 mV), suggesting that saccharin activated a cation conductance. The reversal potential of the saccharin-induced current was -17 +/- 2 mV (n = 10). Intracellular dialysis of 0.5 mM guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S) completely blocked the saccharin-induced response, suggesting the involvement of a G protein in the transduction. The dialysis of heparin (1 mg/mL) also inhibited the response almost completely, but the dialysis of 1 mM 8-Br-cAMP did not affect the response significantly. Intracellular 50 microM inositol 1,4,5-trisphosphate (1,4,5 InsP(3)) also induced the inward current in five (38%) of 13 rod cells, but intracellular Pasteurella multocida toxin (5 microg/mL, G alpha q-coupled PLC activator) did not elicit any response in the cells. The results suggest that saccharin mainly activates a cation conductance in frog taste cells through the mediation of IP3 production.