Title
I<inf>KD</inf> Current in cold transduction and damage-triggered cold hypersensitivity
Date Issued
01 January 2017
Access level
metadata only access
Resource Type
book part
Author(s)
González A.
Herrera G.
Ugarte G.
Restrepo C.
Piña R.
Pertusa M.
Orio P.
Madrid R.
Publisher(s)
Springer New York LLC
Abstract
In primary sensory neurons of the spinal and trigeminal somatosensory system, cold-sensitivity is strongly dependent on the functional balance between TRPM8 channels, the main molecular entity responsible for the cold-activated excitatory current, and Shaker-like Kv1.1-1.2 potassium channels, the molecular counterpart underlying the excitability brake current IKD. This slow-inactivating outward K+ current reduces the excitability of cold thermoreceptor neurons increasing their thermal threshold, and prevents unspecific activation by cold of neurons of other somatosensory modalities. Here we examine the main biophysical properties of this current in primary sensory neurons, its central role in cold thermotransduction, and its contribution to alterations in cold sensitivity triggered by peripheral nerve damage.
Start page
265
End page
277
Volume
1015
Language
English
OCDE Knowledge area
Neurociencias
Subjects
Scopus EID
2-s2.0-85032575893
PubMed ID
Source
Advances in Experimental Medicine and Biology
ISSN of the container
00652598
Sponsor(s)
Fig. 14.4 Mathematical model of CSNs with different densities of IKD and ITRPM8. (a-e) Firing rate (left) and voltage trace (right) of model CSNs with different densities of IKD current and ITRPM8 in response to the cooling stimulus depicted at the top. The Kv1.1–1.2 (gKD) and TRPM8 (gTRPM8) maximum conductance configurations are indicated at left in mS/cm2. Note the shift of the thermal threshold to higher temperatures induced by a reduction of IKD density (d versus c), and the response to cold induced in a cold-insensitive neuron when IKD density is reduced (b versus a), even with a very low density of ITRPM8 (Modified from González et al. 2017) Fig. 14.5 Cold detection mechanisms and role of IKD in thermal sensitivity of primary sensory neurons. (a) Schematic representation of cold detection thresholds and mechanisms in primary somatosensory neurons under physiological conditions. Nerve endings depict TRPM8 and IKD as the main molecular mechanisms involved in the detection of cold stimuli in three functional subtypes of peripheral sensory neurons. The temperature thresholds at which these nerve endings would be excited by temperature drops are shown by the thermometers at the top. The size of labels reflects the relative density of the channels responsible for I cold (TRPM8) and IKD (Kv1.1–1.2) in the different subclasses of sensory neurons. (b) Schematic representation of simultaneous recording of membrane potential (top trace) and temperature (bottom trace) during cooling ramps in one CIN (left panel) and two CSNs (middle and right panel). (c) Schematic representation of the thermal threshold in these sensory neurons in injured mice, shifted to higher temperatures by the reduction of IKD. After axonal damage, the reduction in the functional expression of IKD would recruit a subpopulation of polymodal nociceptors normally activated by noxious cold temperatures that will respond to mild cold. HT-CSNs will respond to innocuous cold temperatures signaling cold discomfort. LT-CSNs expressing low levels of IKD would remain largely unaffected. We propose that, after injury, the reduction in the functional expression of IKD increases the cold sensitivity of HT-CSNs signaling cold discomfort and recruits polymodal nociceptors normally activated by extremely cold temperatures that cause pain Acknowledgements Supported by Grants FONDECYT 1161733 and 1131064( RM), CONICYT ACT-1113 (RM, PO, MP, GU), FONDECYT 1130862 (PO), FONDECYT 11130144 (MP) and FONDECYT 3150431 (AG). GH holds a CONICYT PhD fellowship. RM thanks Dr. F.V iana and VRIDEI-USACH.W e also thank Dr. J. Gómez-Sánchez for his contribution. RM&MP Lab thanks R. Pino and M. Campos for excellent technical assistance. The Centro Interdisciplinario de Neurociencia de Valparaí o is a Millennium Science Institute funded by the Ministry of Economy, Chile. MiNICAD is a Millennium Science Nucleus funded by the Ministry of Economy, Chile.
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