Biomedical Engineering Reference
In-Depth Information
AC—adenylyl cyclase; CNG channel—cyclic nucleotide-gated channel;
PDE—phosphodiesterase; PKA—protein kinase A; ORK—olfactory receptor
kinase; RGS—regulator of G proteins (but here acts on the AC); CaBP—cal-
modulin-binding protein. Green arrows indicate stimulatory pathways; red indi-
cates inhibitory (feedback).
The odor molecule has bound with receptor; a cascade of events is initiated that
transforms the chemical energy of binding into a neural signal that is due to change
in the membrane potential of the olfactory sensor neuron. Even though still dif-
ficult to understand this process but it is mainly well understood in mammals and
humans. G-s family of protein (Family of G proteins) Receptor activates by
receptor which in turn activates adenylyl cyclase. The abundant intracellular
molecule ATP is converted into cyclic AMP (molecule that has numerous sig-
naling roles in cells) by the cyclase. The cyclic AMP binds to the intracellular
cation selective (Na + ,K + ,Ca 2+ ) channel from the inside of the membrane. This
channel is known as cyclic-nucleotide gated (CNG) channels which is closely
related and found in photoreceptors. The influx of Na + and Ca 2+ ions causes the
inside of the cell to become less negative when the CNG channels are open. If
required CNG channels are open for long time, causing the membrane potential to
become less negative and near about the cell threshold and generates an action
potential. The axon circulated the action potential which crosses through a thin
bone known as the cribiform plate, and into the forebrain where it synapses with
second order neurons in the olfactory bulb. Cascade of enzymes provides ampli-
fication and integration of odor-binding events done by second messenger. A
bound odor activated one membrane receptor which in turn activates tens of G
proteins, each of which will activate a cyclase molecule capable of producing
about a thousand molecules of cAMP per second.
To open a channel, cAMP molecules are required but hundreds of thousands of
ions can cross the membrane through a single open channel. So, to produce a
measurable electrical event in an OSN few channels opening together required and it
could pass sufficient current to induce action potential generation [ 6 , 7 ]. Addition to
this pathway, a somewhat unique amplification mechanism is implemented in
OSNs. Through CNG channel the calcium ions are entering and it's able to activate
another ion channel that is absorbent to the negatively charged chloride ion [ 8 ].
Inhibitory responses mediate in Neuronal through Cl - channels, and Cl - ions
enter the cell through an open channel. OSNs maintain high intracellular Cl -
concentration such that there is a Cl - efflux when these channels are activated. Net
positive charge is on the left behind of membrane that further depolarizes the cells,
so adding to the excitatory response magnitude. This interesting revision to the fact
that the olfactory cilia reside in the mucus, outside the body proper and where
concentrations of ions are not as well regulated as they are in normal interstitial
compartments [ 9 , 10 ]. Thus the OSN maintain its own Cl -
battery, if in case the
insufficient threshold current is not provided by Na +
gradient in the mucus, this
will uses to boost the response.
Through a negative feedback pathway involving Calcium ions entering through
the CNG channels are also important in response adaptation [ 11 ]. A calcium ion
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