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In collaboration with Pamela Abshire and Gabrielle Ronnett at Johns Hopkins, we are researching the possibility of using olfactory sensory neurons cultured on chip to detect odorants. The motivations for this are four-fold.
- The binding event is amplified in the cell.
Odorant binding activates a biochemical amplification that results in an action potential (AP). OSNs contain an olfactory-specific G-protein (Golf), tens of which are activated upon odorant binding. In turn, this activates adenylate cyclase, which catalyzes the conversion of adenosine triphosphate (ATP) into a neurotransmitter, cyclic AMP (cAMP). A single activated enzyme can convert a large number of ATPs (1000/second). The increase in cAMP opens ion channels that permit Na+ and Ca2+ to enter the cell, depolarizing the neuron and triggering an AP, which can readily be detected extracellularly.
- Use of OSNs provides a large dynamic range due to adaptation.
OSNs “adapt” and reduce the rate of action potentials in response to the continued presence of an odorant. Adaptation occurs because of: (1) increased Ca2+ binding by the protein calmodulin, decreasing the sensitivity of the channel to cAMP; and (2) the extrusion of Ca2+ through the activation of Na+/Ca2+ exchange proteins that reduce the amplitude of the receptor potential.
- The cells provide the “infrastructure” for maintaining the receptors.
Cells regulate and repair themselves to maintain normal function (homeostasis).
- OSNs produce an electrical signal (action potential) upon odorant binding.
These signal can be detected extra-cellularly, and the number of APs is correlated with the odorant concentration.
These characteristics mean that biological olfactory sensors have no equal in human-made devices.
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