The site-specific, bi-directional regulation of tau phosphorylation warrants further studies on evaluation of dose and time dependent effects on OGA inhibition. The EOG was recorded SB431542 ALK inhibitor between a glass microelectrode filled with Ringer that touched the surface of a turbinate and the reference electrode. The micromanipulatorallowed the microelectrode to be withdrawn and repositioned repeatedly to the same location on a turbinate. Electrical signals were amplified by a high-impedance preamplifier. The amplified signal was digitized and visualized on a PC using Igor Pro 4 software. 100-ms pulses of air at 10 psi, odorized by passing through a vial containing 99% isoamyl acetate, were directed at the turbinates using a Picospritzer II. A 100-ms pulse of non-odorized air was applied about 5 s before the odorant. Since the response evoked by non-odorized air was a small fraction of the response to the odorant, the EOG amplitudes were not corrected for this. Our criteria for including the EOGs recorded were that the control EOG was at least 2 mV in amplitude and had a time constant of recovery from the peakof less than 1 s. Successive stimuli were separated by at least 2 min. After locating an area of a turbinate that produced an acceptable EOG, the recording electrode was withdrawn. Ringer was applied to the turbinates, left for about 5 min covering the turbinates, and then wicked away. The electrode was repositioned in WZ4002 contact with the same area and several control EOGs were recorded. After applying and wicking a solution from a 
turbinate, the amplitude of the EOG was initially reduced but recovered substantially. Wicking was not able to remove all the added liquid and the change in amplitude was presumably due to the increased thickness of the unstirred layer covering the receptive surface. This layer of liquid could reduce access of the odorant to the tissue and/or could reduce the density of EOG currents. As liquid evaporated or drained off, the EOG amplitude recovered. The amplitude and time constant of the third EOG following a Ringer treatment were usually used for analysis. The electrode was withdrawn again, and the test solution, either Li + -replaced Ringer or Ringer containing 100 mM or 500 mM caloxin, was applied and left for about 5 min covering the turbinates and then wicked. The electrode was repositioned again in contact with the same area and EOGs recorded as above. The recording electrode was withdrawn again and the turbinates were rinsed 3 times with Ringer and then additional Ringer applied for 5 min, wicked, and the EOG recorded again. For a given test solution, only one such experimental series was done on a given turbinate. In some experiments, the second side of the head was also used. The control EOG in every run met the criteria given above for amplitude and time constant. Regardless of the treatment, the recovery of the EOG amplitude from its peak after application of a solution was somewhat variable. One likely source of variability was the exact position of the recording electrode on a turbinate. For example, when recording from a more caudal position on a turbinate, it may have been more difficult to get rid of excess fluid. This might have led to a decrease in the amplitude of the EOG. Based on visual inspection, the rostral portions of turbinates tended to dry out sooner than the caudal portions. To investigate whether PMCA contributes to termination of the odor response, we tested one of the caloxins, a class of selective inhibitors of PMCA. Of the several caloxins available, we selected caloxin 1b1, which has activity against all four PMCA isoforms.