A NOVEL

MECHANOSENSITIVE
CHANNEL IDENTIFIED IN
SENSORY NEURONS
Taycia Grasmick

Highlighting the research of Hawon Cho, Hae

Yeon Koo, Sangsung Kim, Sung Pyo Park,
Youngduk Yang and Uhtaek Oh
Mechanosensitive (MS) channels are ion gated channels
associated with the perception of touch, pressure, proprioception,
and pain.
Traditionally two types of mechanoreceptors described, low
threshold (LT), pressure greater than 20 mmHg, and high threshold
(HT), pressures up to 60 mmHg.
However, diverse responses to stimuli suggest other
mechanoreceptors must exist.
Proposed new (MS) channel, low threshold small conductance
(LTSC) channel.

BACKGROUND
 Cultured DRGs dissected from lumbar and thoracic spinal cords of neonatal rats
Ganglia washed and treated to prevent contamination, interference, and health of target neurons.
Electrophysiology data collected to detect electrochemical changes in the neuron through stimulation in
patches containing only one or two channels.
Membrane stretch was accomplished using mercury connected to a patch pipette and then positive or
negative pressures applied, mmHg.

MATERIALS AND METHODS

▶ Borosilicate glass pipettes coated with Sylgard used to apply
gently suction on the neuron cultured to have a giga-seal.
▶ Tip resistance: 3 MΩ for recording single-channel currents
▶ With cell attached, outside-out and inside-out patches were formed.
▶ Recorded with a patch-clamp amplifier and filtered at 5 kHz with a low-pass
Bessel filter.
▶ Pressure applications were measured by the differences in the
height of mercury columns in the manometer, in mmHg.

ELECTROPHYSIOLOGY AND PRESSURE

APPLICATION
▶ Activation of MS single-channel currents
▶ Revealed presence of channels (LTSC) with amplitudes much smaller than
those of LT channels, but much greater than those of HT channels,
supporting hypothesis.
▶ Pressure-response relationship
▶ Discovered high sensitivity to negative pressures, 9.8 ± 0.6 mmHg, far lower
than LT and HT.
▶ Current-voltage (I-V) relationship
▶ Kinetic analyses helped determine that negative pressures of -80 mmHg
increased the long and short openings significantly, with the inverse also
being true.

ACTIVATION OF MS SINGLE-CHANNEL
CURRENTS
▶ Separate baths containing Na+, Li+, K+ or Cs+
▶ Looking for LTSC potentials in response to the presence of the
cations.
▶ Nonselective cation channel: Channel was found to be
permeable to each of the monovalent cations and Ca+ when
placed in a bi-ionic solution. It did not discriminate Na+ from any
of the other ions listed.
▶ Inhibitor: Gd3+ block tested and found to greatly inhibit the LTSC
channel as it does the LT and HT channels.

ION SELECTIVITY
▶ Excision did not impact the function of LTSC channels, as it does
with LT and HT channels.
▶ Amiloride and arachidonic acid did not negatively impact the
function of LTSC channels, as it does LT and HT channels.
▶ Prostagandins (PGE2) seems to sensitize, via a protein kinase, A
(PKA) pathway, as in HT MSs.
▶ Cell size distribution is greatest in small-to-medium sized DRG
neurons, with fewest in the larger cells.

FURTHER COMPARATIVE ANALYSIS

▶ LTSC is distinct form LT and HT MSs.
▶ Activated by stretch imposed on the patch membrane in DRG
neurons
▶ Quite low pressure sensitivities
▶ Significantly small single-channel conductance
▶ Linear I-V relationship
▶ Sensitized by application of PGE2
▶ Unique current amplitudes

CONCLUSION
▶ Identification of a specific role in mediating specific types of
mechanical sensation until a genetic identity is revealed.
▶ Cell-size lends itself into further research into the specific types of
neurons equipped with LTSC MSs, in order to further understand
their role.
▶ Research may yet find that LTSCs are another order of LT MSs.
▶ LTSC is likely to play a role in mechanotransduction of high
intensity mechanical, including noxious, stimuli.

PROJECTIONS
▶ Cho, H., Koo, J. Y., Kim, S., Park, S. P., Yang, Y., & Oh, U. (2006). A
novel mechanosensitive channel identified in sensory
neurons. The European Journal Of Neuroscience, 23(10), 2543-
2550.

REFERENCES