taste/olfaction
N |
• homozygotes exhibit normal development of the olfactory epithelium and olfactory bulb relative to wild-type mice
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• cAMP-activated currents recorded in inside-out membrane patches excised from dendritic knobs of mutant olfactory receptor neurons (ORNs) indicate a decreased affinity for cAMP, with a dose-response relation shifted by ~10-fold to higher cAMP concentrations
• electro-olfactograms (EOGs) recorded in response to a 500-ms pulse of isobutyl methyl xanthine (IBMX), which increases intracellular cAMP by inhibiting endogenous phosphodiesterase activity, indicate a ~3-fold shift in the IBMX dose-response relation to a higher IBMX concentration
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• homozygotes exhibit a striking reduction in the rate of adaptation of the electrophysiological response to odors in ORNs because of defective Ca2+-calmodulin-mediated channel desensitization
• EOG recordings from the olfactory epithelium in response to a long (8-sec) odor stimulus (cineole, 100 M) indicate a significant reduction in the desensitization rate, with similar results obtained in a paired-pulse paradigm (cineole, 100 M, 500 ms) and when IBMX is used as a stimulus
• in response to 50 M Ca2+ and 1 M CaM, channels in excised membrane patches from mutant mice display a 70-fold slower Ca2+-CaM-induced inhibition along with a several-fold faster current recovery relative to wild-type channels
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