Transcript HairCellTransductionx

Hair Cell Transduction
Electron micrograph of 3 OHCs
(from Kimura,
1966)
spiral ligament
modiolus
When the basilar membrane vibrates up
and down in response to the sound wave,
the hair cell cilia are displaced 1st in one
direction then in the other; i.e., 1st away
from the modiolus, then toward it.
To state it differently, the cilia move 1st in
the direction of the taller hairs, then in the
direction of the shorter hairs.
(Note: Shown here are OHCs, which is not
inaccurate, but it is exactly this behavior
in the IHCs that is of the greatest interest
since the IHCs rather than the OHCs are
the site of hair cell transduction.)
Transduction Links:
Thin filaments that
connect adjacent
cilia.
Note that the simplified drawing here shows a single afferent fiber
and a single efferent fiber. This is misleading. For the all-important
IHCs, there are very few efferent fibers and many afferent fibers
synapsing on a single cell (on average ~10 per IHC).
Short digression: Differences in innervation patterns for IHCs vs OHCs
(from Spoendlin,1979)
A single IHC is typically innervated by
many nerve fibers (nearly all of them
afferent). To simplify the figure,
innervation is show for just one IHC,
but they all look like this.
OHCs are just the opposite: Nerve
fibers branch and typically innervate
many OHCs. Also, most of the efferent
fibers synapse on OHCs rather than
IHCs.
Another view of transduction links. They are shown
in this schematic figure as tiny springs – which is
how they behave (though not how they look).
modiolus
spiral ligament
Transduction links
(from Fabio Mammano)
+40 mV (resting
potential of
endolymph)
-80 mV
Intracellular
resting potential
Together, the -80 mV potential inside the HC and the
+40 mV potential outside the HC (i.e., in the
endolymph) create two terminals of a 120 mV battery.
When the short cilia move
in the direction of the tall
cilia, the transduction
links are stretched.
When the tall cilia move in
the direction of the short
cilia, the transduction links
are compressed.
Compressing the link
squeezes the ion channel
closed, inhibiting current
flow.
Stretching the link opens
an ion channel, allowing
current to flow.
Note that the ion
channel (also called a
molecular gate) is not
either open or closed.
Large movement of the
cilia pulls the channel
way open; small
movement pulls it just a
little open. This is called
a graded response or a
continuous response –
not all or none.
1. The flow of positive ions into
the hair cell body is called the
receptor current.
2. The receptor current stimulates
the release of neurotransmitter
chemicals from the hair cell into
the tiny synaptic junction at the
base of the hair cell.
3. The uptake of neurotransmitter chemicals by the
adjacent nerve fibers stimulates
the firing of the fibers – though
this process is probabilistic
rather than deterministic (more
later).
Another view of ion flow being regulated by the
movement of cilia in just one direction: Short hairs
moving in the direction of long hairs, opening the
molecular gate (not shown) and allowing positive ions
(the yellow stuff in the animation below) to flow into
the hair cell.
The receptor current is graded or continuous, completely unlike
the all-or-none behavior of neurons. What does that mean?
Just this:
when the instantaneous amplitude of the signal is large
the displacement of the basilar membrane will be large
the displacement of the hair cell cilia will be large
the receptor current will be large (because the molecular gate
or ion channel will be way open)
the quantity of neurotransmitter chemicals dumped into the
synaptic junction will be large
and finally, the probability of a pulse on the 8th N will be high
(not certain)
BUT:
The 8th N fiber will either fire or not, in its usual all-or-none
fashion
Similarly:
when the instantaneous amplitude of the signal is small
the displacement of the basilar membrane will be small
the displacement of the hair cell cilia will be small
the receptor current will be small (because the molecular
gate or ion channel will be just slightly open)
the quantity of neurotransmitter chemicals dumped into the
synaptic junction will be small
and finally, the probability of a pulse on the 8th N will be low
(not zero)
BUT once again:
The 8th N fiber will either fire or not, in its usual all-or-none
fashion
Variable resistor:
hair-cell cilia
Neg. terminal: hair
cell body (~-80 mV)
Way Simplified Hair Cell
Circuit
(Note: The meter
is there just to
show us what
current is. There’s
not really a
current meter in
your ear.)
~120 mV
Pos. terminal: endolymph (+40 mV)
Important: These values (+40 & -80 mV) are resting
potentials: This is what the electrical potentials (voltages)
measure when the HC is not being stimulated.
(Brief Digression)
Hallowell Davis
Hallowell Davis, former director of the
Central Institute for the Deaf in St. Louis,
and a pioneer in hearing research. In
1939 Hallowell Davis and Robert
Galambos made the 1st recordings of the
electrical activity of individual neurons.
That’s 1939 – the year in which, among
many other things, WWII started and
The Wizard of Oz (a nearly perfect movie) and
Gone with the Wind (a terrible movie, according
to at least one crackpot) were released. Our
understanding of hair cell physiology has
advanced enormously since Davis’ early
work, but current models of hair cell
function are very closely related to a
model described by Davis in 1963.
Relationship between the input signal and the receptor
current for a sinusoid (left) and a complex periodic signal
(right).
Note that the 2 receptor current and the input signal look
similar, except that the bottom half is missing. This is called
half-wave rectification.
Why is the bottom half of the signal missing in the receptor
current?
Input Signal
Input Signal
Receptor Current
Receptor Current
OHCs: Why do we have them at all? Transduction is
carried out by the IHCs, right? What’s the point of
having OHCs?
watch this cell
Phenomenon is called hair-cell motility (motility=movement).
Only mammals have evolved HCs that exhibit this kind of
motility. Why?
Frequency ranges for a few mammals (with OHCs)
Whales:
Bats:
Humans:
20 - 100,000 Hz
1,500 - 100,000 Hz
20-20,000 Hz
Frequency ranges for a few non-mammals (without OHCs)
Frogs:
Fish:
Crickets:
Birds:
600 – 3,000 Hz
20 – 3,000 Hz
500 – 5,000 Hz
Variable across species, but top
end usually well below 10,000 Hz
What’s the big difference? (A: Much improved high freq hearing)
For what purpose did mammals evolve OHCs?