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Cellular and Ion Channel Mechanisms Underlying the Sense of Light Touch in Mammals

Award Number: R01DE023090
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/12/2013
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Cellular and Ion Channel Mechanisms Underlying the Sense of Light Touch in Mammals - ABSTRACT: The sense of touch is critical for daily tasks including tactile discrimination, social interaction, and environmental exploration. The overall objective of this project is to identify the cellular and molecular mechanisms underlying the sense of touch in mammals. Previous studies have shown that Merkel discs, a main type of tactile end organ, play a central role in the sense of touch. Merkel discs are located in touch sensitive spots throughout the body especially at human fingertips and whisker hair follicles of non-primate mammals. A Merkel disc consists of a Merkel cell and an Aβ-afferent ending (Merkel ending) to form a synapse-like structure. We and others have previous shown that the Piezo2 channel on Merkel cells is the sensor of touch. We have further shown that tactile stimuli activate Piezo2 channels in Merkel cells to result in Ca2+-action potentials, which leads to Aβ-afferent impulses and behavioral tactile responses. However, the mechanism by which tactile-induced excitatory signals on Merkel cells are transmitted to Merkel endings remains elusive and is the focus of this renewal application. Our central hypothesis is that acid sensing ion channels (ASICs) are the excitatory postsynaptic receptors and proton is the principal transmitter to mediate excitatory postsynaptic currents (EPSCs) and synaptic transmission at Merkel discs. We will test this novel hypothesis with the following specific aims. Aim 1. Characterize the fundamental nature of EPSCs at Merkel endings of Aβ-afferent fibers. Aim 2. Demonstrate that EPSCs are mediated by ASICs located at Merkel endings. Aim 3. Elucidate that activation of ASICs by protons is responsible for the generation of EPSCs at Merkel endings. Aim 4. Identify the isoform of functional ASICs that mediate EPSCs at Merkel endings. Pressure-patch-clamp recordings will be applied at the heminode of Merkel endings in rodent whisker hair follicles to record EPSCs that are evoked by mechanical stimulation, and other techniques including synaptic physiology, pharmacology, immunohistochemistry, and mouse genetics will be used to achieve the above aims. By completing the above aims, we will have uncovered a new fundamental mechanism mediating synaptic transmission of tactile signals at Merkel discs. This will significantly advance scientific knowledge about molecular mechanisms underlying the sense of touch. It may also have important implications in mechanical sensory dysfunctions (e.g., loss of touch sensation) seen under clinical conditions such as diabetes and chemotherapy.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $499,348 )
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	000	14	6/2/2025	NON-COMPETING CONTINUATION	$499,348
														Subtotal = $499,348

Issue Date FY: 2024 ( Subtotal = $489,359 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	001	13	7/10/2024	NON-COMPETING CONTINUATION	$39,946
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	000	13	5/15/2024	NON-COMPETING CONTINUATION	$449,413
2024	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	003	12	8/2/2024	COMPETING CONTINUATION	$268,720
2024	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	002	11	8/2/2024	NON-COMPETING CONTINUATION	-$268,720
														Subtotal = $489,359

Issue Date FY: 2023 ( Subtotal = $506,731 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	002	12	6/12/2023	COMPETING CONTINUATION	$506,731
2023	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	001	11	6/5/2023	NON-COMPETING CONTINUATION	$0
2023	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	000	11	10/25/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $506,731

Issue Date FY: 2021 ( Subtotal = $439,325 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	000	11	8/9/2021	NON-COMPETING CONTINUATION	$439,325
														Subtotal = $439,325

Issue Date FY: 2020 ( Subtotal = $439,325 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	000	10	8/14/2020	NON-COMPETING CONTINUATION	$439,325
														Subtotal = $439,325

Issue Date FY: 2019 ( Subtotal = $439,325 )
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	000	9	8/1/2019	NON-COMPETING CONTINUATION	$439,325
														Subtotal = $439,325

Issue Date FY: 2018 ( Subtotal = $439,325 )
2018	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	005	8	8/1/2018	NON-COMPETING CONTINUATION	$439,325
2018	2017	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	002	7	2/5/2018	COMPETING CONTINUATION	$414,108
2018	2017	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	004	7	4/20/2018	COMPETING CONTINUATION	-$2,805
2018	2017	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	001	6	2/5/2018	NON-COMPETING CONTINUATION	-$367,500
2018	2016	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	003	5	4/20/2018	NON-COMPETING CONTINUATION	$2,805
2018	2016	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	000	5	2/5/2018	NON-COMPETING CONTINUATION	-$46,608
														Subtotal = $439,325

Issue Date FY: 2017 ( Subtotal = $806,825 )
2017	2017	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	002	7	9/14/2017	COMPETING CONTINUATION	$439,325
2017	2017	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	000	6	7/19/2017	NON-COMPETING CONTINUATION	$367,500
2017	2017	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	001	6	9/14/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $806,825

Issue Date FY: 2016 ( Subtotal = $367,500 )
2016	2016	UNIVERSITY OF ALABAMA AT BIRMINGHAM	1530 3rd Avenue South, AB 1170	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	000	5	6/28/2016	NON-COMPETING CONTINUATION	$367,500
														Subtotal = $367,500

Issue Date FY: 2015 ( Subtotal = $374,585 )
2015	2015	UNIVERSITY OF ALABAMA AT BIRMINGHAM	1530 3rd Avenue South, AB 1170	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	002	4	6/19/2015	NON-COMPETING CONTINUATION	$367,500
2015	2014	UNIVERSITY OF ALABAMA AT BIRMINGHAM	1530 3rd Avenue South, AB 1170	BIRMINGHAM	AL	35294	JEFFERSON	USA	Oral Diseases and Disorders Research	001	3	3/19/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$367,500
2015	2014	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	45221	HAMILTON	USA	Oral Diseases and Disorders Research	000	2	3/18/2015	NON-COMPETING CONTINUATION	-$360,415
														Subtotal = $374,585

Issue Date FY: 2014 ( Subtotal = $396,250 )
2014	2014	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	45221	HAMILTON	USA	Oral Diseases and Disorders Research	000	2	6/4/2014	NON-COMPETING CONTINUATION	$396,250
														Subtotal = $396,250

Issue Date FY: 2013 ( Subtotal = $396,250 )
2013	2013	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	45221	HAMILTON	USA	Oral Diseases and Disorders Research	000	1	6/26/2013	NEW	$396,250
														Subtotal = $396,250

Grand Total All Awards = $5,594,148

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Cellular and Ion Channel Mechanisms Underlying the Sense of Light Touch in Mammals

Award Number: R01DE023090

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/12/2013

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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